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Sample records for aerobic mitochondrial energy

  1. Mitochondrial Energy-Deficient Endophenotype in Autism

    Directory of Open Access Journals (Sweden)

    J. J. Gargus

    2008-01-01

    Full Text Available While evidence points to a multigenic etiology of most autism, the pathophysiology of the disorder has yet to be defined and the underlying genes and biochemical pathways they subserve remain unknown. Autism is considered to be influenced by a combination of various genetic, environmental and immunological factors; more recently, evidence has suggested that increased vulnerability to oxidative stress may be involved in the etiology of this multifactorial disorder. Furthermore, recent studies have pointed to a subset of autism associated with the biochemical endophenotype of mitochondrial energy deficiency, identified as a subtle impairment in fat and carbohydrate oxidation. This phenotype is similar, but more subtle than those seen in classic mitochondrial defects. In some cases the beginnings of the genetic underpinnings of these mitochondrial defects are emerging, such as mild mitochondrial dysfunction and secondary carnitine deficiency observed in the subset of autistic patients with an inverted duplication of chromosome 15q11-q13. In addition, rare cases of familial autism associated with sudden infant death syndrome (SIDS or associated with abnormalities in cellular calcium homeostasis, such as malignant hyperthermia or cardiac arrhythmia, are beginning to emerge. Such special cases suggest that the pathophysiology of autism may comprise pathways that are directly or indirectly involved in mitochondrial energy production and to further probe this connection three new avenues seem worthy of exploration: 1 metabolomic clinical studies provoking controlled aerobic exercise stress to expand the biochemical phenotype, 2 high-throughput expression arrays to directly survey activity of the genes underlying these biochemical pathways and 3 model systems, either based upon neuronal stem cells or model genetic organisms, to discover novel genetic and environmental inputs into these pathways.

  2. Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

    International Nuclear Information System (INIS)

    High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl2), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl2 supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl2 supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl2 supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl2 for 15 days along with training. ► CoCl2 supplementation augmented

  3. Plasma cell‐free mitochondrial DNA declines in response to prolonged moderate aerobic exercise

    OpenAIRE

    Shockett, Penny E.; Khanal, Januka; Sitaula, Alina; Oglesby, Christopher; Meachum, William A.; Castracane, V. Daniel; Kraemer, Robert R.

    2016-01-01

    Abstract Increased plasma cell‐free mitochondrial DNA (cf‐mDNA), a damage‐associated molecular pattern (DAMP) produced by cellular injury, contributes to neutrophil activation/inflammation in trauma patients and arises in cancer and autoimmunity. To further understand relationships between cf‐mDNA released by tissue injury, inflammation, and health benefits of exercise, we examined cf‐mDNA response to prolonged moderate aerobic exercise. Seven healthy moderately trained young men (age = 22.4 ...

  4. Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

    International Nuclear Information System (INIS)

    Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (TDR) cells from tumors. We demonstrate that TDR cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage

  5. Influence of aerobic exercise intensity on myofibrillar and mitochondrial protein synthesis in young men during early and late postexercise recovery

    OpenAIRE

    Di Donato, Danielle M.; Daniel W D West; Churchward-Venne, Tyler A.; Breen, Leigh; Baker, Steven K.; Phillips, Stuart M.

    2014-01-01

    Aerobic exercise is typically associated with expansion of the mitochondrial protein pool and improvements in muscle oxidative capacity. The impact of aerobic exercise intensity on the synthesis of specific skeletal muscle protein subfractions is not known. We aimed to study the effect of aerobic exercise intensity on rates of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis over an early (0.5–4.5 h) and late (24–28 h) period during postexercise recovery. Using a within-subje...

  6. Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

    Energy Technology Data Exchange (ETDEWEB)

    Saxena, Saurabh [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India); Shukla, Dhananjay [Department of Biotechnology, Gitam University, Gandhi Nagar, Rushikonda, Visakhapatnam-530 045 Andhra Pradesh (India); Bansal, Anju, E-mail: anjubansaldipas@gmail.com [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)

    2012-11-01

    High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl{sub 2} for 15 days along with training. ► Co

  7. Cerebral energy metabolism during induced mitochondrial dysfunction

    DEFF Research Database (Denmark)

    Nielsen, T H; Bindslev, TT; Pedersen, S M;

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  8. Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise.

    Science.gov (United States)

    Shockett, Penny E; Khanal, Januka; Sitaula, Alina; Oglesby, Christopher; Meachum, William A; Castracane, V Daniel; Kraemer, Robert R

    2016-01-01

    Increased plasma cell-free mitochondrial DNA (cf-mDNA), a damage-associated molecular pattern (DAMP) produced by cellular injury, contributes to neutrophil activation/inflammation in trauma patients and arises in cancer and autoimmunity. To further understand relationships between cf-mDNA released by tissue injury, inflammation, and health benefits of exercise, we examined cf-mDNA response to prolonged moderate aerobic exercise. Seven healthy moderately trained young men (age = 22.4 ± 1.2) completed a treadmill exercise trial for 90 min at 60% VO2 max and a resting control trial. Blood was sampled immediately prior to exercise (0 min = baseline), during (+18, +54 min), immediately after (+90 min), and after recovery (R40). Plasma was analyzed for cf-mDNA, IL-6, and lactate. A significant difference in cf-mDNA response was observed between exercise and control trials, with cf-mDNA levels reduced during exercise at +54 and +90 (with or without plasma volume shift correction). Declines in cf-mDNA were accompanied by increased lactate and followed by an increase in IL-6, suggesting a temporal association with muscle stress and inflammatory processes. Our novel finding of cf-mDNA decline with prolonged moderate treadmill exercise provides evidence for increased clearance from or reduced release of cf-mDNA into the blood with prolonged exercise. These studies contrast with previous investigations involving exhaustive short-term treadmill exercise, in which no change in cf-mDNA levels were reported, and contribute to our understanding of differences between exercise- and trauma-induced inflammation. We propose that transient declines in cf-mDNA may induce health benefits, by reducing systemic inflammation. PMID:26755735

  9. Research on the Characteristic of Energy Metabolism of Aerobics Sports and Reasonable Nutrition Supplement

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    Shuang Cheng

    2015-07-01

    Full Text Available The reasonable nutrition problem has received extensive attention. In this study, it takes the characteristics of aerobics sports as the breakthrough point, by analyzing the characteristics of energy metabolism of aerobics; it explains the composition of three large energy systems of energy metabolism, then discusses the nutritional requirements of Fitness Aerobics as well as the reasonable nutrition supplement measures.

  10. Research on the Characteristic of Energy Metabolism of Aerobics Sports and Reasonable Nutrition Supplement

    OpenAIRE

    Shuang Cheng

    2015-01-01

    The reasonable nutrition problem has received extensive attention. In this study, it takes the characteristics of aerobics sports as the breakthrough point, by analyzing the characteristics of energy metabolism of aerobics; it explains the composition of three large energy systems of energy metabolism, then discusses the nutritional requirements of Fitness Aerobics as well as the reasonable nutrition supplement measures.

  11. Energy efficient aerobic treatment of forest industry wastewaters; Energieffektiv aerob rening av skogsindustriella avloppsvatten

    Energy Technology Data Exchange (ETDEWEB)

    Sandberg, Maria; From-Aldaron, Mattias

    2011-01-15

    There is great potential to reduce energy requirements in aerobic biological purification if the oxygen demand can be reduced and oxygen delivery, when process water is aerated, is made more efficient. A model was developed to estimate the possible reduction in oxygen demand. Model variables were COD reduction, sludge withdrawal, oxygen, and alpha-value. Attempts made in an aerator in the lab-scale process shows that water content strongly affects oxygen transport and alpha-value. Surface active extract substances such as fatty acids and resin acids have greatest significance. The effect increases with the concentration of extract substances and decreases with added sodium chloride content

  12. Mitochondrial uncoupling proteins and energy metabolism

    Directory of Open Access Journals (Sweden)

    Rosa Anna Busiello

    2015-02-01

    Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

  13. Expression of a functional oxygen-labile nitrogenase component in the mitochondrial matrix of aerobically grown yeast

    Science.gov (United States)

    López-Torrejón, Gema; Jiménez-Vicente, Emilio; Buesa, José María; Hernandez, Jose A.; Verma, Hemant K.; Rubio, Luis M.

    2016-01-01

    The extreme sensitivity of nitrogenase towards oxygen stands as a major barrier to engineer biological nitrogen fixation into cereal crops by direct nif gene transfer. Here, we use yeast as a model of eukaryotic cell and show that aerobically grown cells express active nitrogenase Fe protein when the NifH polypeptide is targeted to the mitochondrial matrix together with the NifM maturase. Co-expression of NifH and NifM with Nif-specific Fe–S cluster biosynthetic proteins NifU and NifS is not required for Fe protein activity, demonstrating NifH ability to incorporate endogenous mitochondrial Fe–S clusters. In contrast, expression of active Fe protein in the cytosol requires both anoxic growth conditions and co-expression of NifH and NifM with NifU and NifS. Our results show the convenience of using mitochondria to host nitrogenase components, thus providing instrumental technology for the grand challenge of engineering N2-fixing cereals. PMID:27126134

  14. Mitochondrial Energy Metabolism and Thyroid Cancers.

    Science.gov (United States)

    Lee, Junguee; Chang, Joon Young; Kang, Yea Eun; Yi, Shinae; Lee, Min Hee; Joung, Kyong Hye; Kim, Kun Soon; Shong, Minho

    2015-06-01

    Primary thyroid cancers including papillary, follicular, poorly differentiated, and anaplastic carcinomas show substantial differences in biological and clinical behaviors. Even in the same pathological type, there is wide variability in the clinical course of disease progression. The molecular carcinogenesis of thyroid cancer has advanced tremendously in the last decade. However, specific inhibition of oncogenic pathways did not provide a significant survival benefit in advanced progressive thyroid cancer that is resistant to radioactive iodine therapy. Accumulating evidence clearly shows that cellular energy metabolism, which is controlled by oncogenes and other tumor-related factors, is a critical factor determining the clinical phenotypes of cancer. However, the role and nature of energy metabolism in thyroid cancer remain unclear. In this article, we discuss the role of cellular energy metabolism, particularly mitochondrial energy metabolism, in thyroid cancer. Determining the molecular nature of metabolic remodeling in thyroid cancer may provide new biomarkers and therapeutic targets that may be useful in the management of refractory thyroid cancers. PMID:26194071

  15. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome.

    Directory of Open Access Journals (Sweden)

    Lance H Rodan

    Full Text Available To study the effects of L-arginine (L-Arg on total body aerobic capacity and muscle metabolism as assessed by (31Phosphorus Magnetic Resonance Spectroscopy ((31P-MRS in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes syndrome.We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR in MTTL1 gene with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine.At baseline (no L-Arg, MELAS had lower serum Arg (p = 0.001. On 3(1P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr (p = 0.05, decreased ATP (p = 0.018, and decreased intracellular Mg(2+ (p = 0.0002 when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1 increase in mean % maximum work at anaerobic threshold (AT (2 increase in % maximum heart rate at AT (3 small increase in VO(2peak. On (31P-MRS the following mean trends were noted: (1 A blunted decrease in pH after exercise (less acidosis (2 increase in Pi/PCr ratio (ADP suggesting increased work capacity (3 a faster half time of PCr recovery (marker of mitochondrial activity following 5 minutes of moderate intensity exercise (4 increase in torque.These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study.Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects.ClinicalTrials.gov NCT01603446.

  16. Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

    OpenAIRE

    Tang, Yan; Luo, Binping; Deng, Zhili; Wang, Ben; Liu, Fangfen; Li, Jinmao; SHI, Wei; Xie, Hongfu; Hu, Xingwang; Li, Ji

    2016-01-01

    Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect ...

  17. Reduction of nuclear encoded enzymes of mitochondrial energy metabolism in cells devoid of mitochondrial DNA

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Edith E., E-mail: ed.mueller@salk.at [Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Muellner Hauptstrasse 48, 5020 Salzburg (Austria); Mayr, Johannes A., E-mail: h.mayr@salk.at [Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Muellner Hauptstrasse 48, 5020 Salzburg (Austria); Zimmermann, Franz A., E-mail: f.zimmermann@salk.at [Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Muellner Hauptstrasse 48, 5020 Salzburg (Austria); Feichtinger, Rene G., E-mail: r.feichtinger@salk.at [Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Muellner Hauptstrasse 48, 5020 Salzburg (Austria); Stanger, Olaf, E-mail: o.stanger@rbht.nhs.uk [Department of Cardiac Surgery, Paracelsus Medical University, Muellner Hauptstrasse 48, 5020 Salzburg (Austria); Sperl, Wolfgang, E-mail: w.sperl@salk.at [Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Muellner Hauptstrasse 48, 5020 Salzburg (Austria); Kofler, Barbara, E-mail: b.kofler@salk.at [Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Muellner Hauptstrasse 48, 5020 Salzburg (Austria)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We examined OXPHOS and citrate synthase enzyme activities in HEK293 cells devoid of mtDNA. Black-Right-Pointing-Pointer Enzymes partially encoded by mtDNA show reduced activities. Black-Right-Pointing-Pointer Also the entirely nuclear encoded complex II and citrate synthase exhibit reduced activities. Black-Right-Pointing-Pointer Loss of mtDNA induces a feedback mechanism that downregulates complex II and citrate synthase. -- Abstract: Mitochondrial DNA (mtDNA) depletion syndromes are generally associated with reduced activities of oxidative phosphorylation (OXPHOS) enzymes that contain subunits encoded by mtDNA. Conversely, entirely nuclear encoded mitochondrial enzymes in these syndromes, such as the tricarboxylic acid cycle enzyme citrate synthase (CS) and OXPHOS complex II, usually exhibit normal or compensatory enhanced activities. Here we report that a human cell line devoid of mtDNA (HEK293 {rho}{sup 0} cells) has diminished activities of both complex II and CS. This finding indicates the existence of a feedback mechanism in {rho}{sup 0} cells that downregulates the expression of entirely nuclear encoded components of mitochondrial energy metabolism.

  18. Muscle 3243A -> G mutation load and capacity of the mitochondrial energy-generating system

    NARCIS (Netherlands)

    Janssen, Antoon J. M.; Schuelke, Markus; Smeitink, Jan A. M.; Trijbels, Frans J. M.; Sengers, Rob C. A.; Lucke, Barbara; Wintjes, Liesbeth T. M.; Morava, Eva; van Engelen, Baziel G. M.; Struts, Bart W.; Hol, Frans A.; Siers, Marloes H.; ter Laak, Henk; van der Knaap, Marjo S.; van Spronsen, Francjan J.; Rodenburg, Richard J. T.; van den Heuvel, Lambert P.

    2008-01-01

    Objective: The mitochondrial energy-generating system (MEGS) encompasses the mitochondrial enzymatic reactions from oxidation of pyruvate to the export of adenosine triphosphate. It is investigated in intact muscle mitochondria by measuring the pyruvate oxidation and adenosine triphosphate productio

  19. Muscle 3243A-->G mutation load and capacity of the mitochondrial energy-generating system.

    NARCIS (Netherlands)

    Janssen, A.J.; Schuelke, M.; Smeitink, J.A.M.; Trijbels, F.J.; Sengers, R.C.; Lucke, B.; Wintjes, L.T.; Morava, E.; Engelen, B.G.M. van; Smits, B.W.; Hol, F.A.; Siers, M.H.; Laak, H. ter; Knaap, M.S. van der; Spronsen, F.J. van; Rodenburg, R.J.; Heuvel, L.P.v.d.

    2008-01-01

    OBJECTIVE: The mitochondrial energy-generating system (MEGS) encompasses the mitochondrial enzymatic reactions from oxidation of pyruvate to the export of adenosine triphosphate. It is investigated in intact muscle mitochondria by measuring the pyruvate oxidation and adenosine triphosphate productio

  20. Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection

    OpenAIRE

    Gonçalves, Renata L. S.; Oliveira, Jose Henrique M.; Oliveira, Giselle A.; Andersen, John F.; Oliveira, Marcus F.; Pedro L Oliveira; Barillas-Mury, Carolina

    2012-01-01

    Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses ...

  1. Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis

    NARCIS (Netherlands)

    Slavov, Nikolai; Budnik, Bogdan A; Schwab, David; Airoldi, Edoardo M; van Oudenaarden, Alexander

    2014-01-01

    Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such ro

  2. Phylogenomic reconstruction indicates mitochondrial ancestor was an energy parasite.

    Science.gov (United States)

    Wang, Zhang; Wu, Martin

    2014-01-01

    Reconstruction of mitochondrial ancestor has great impact on our understanding of the origin of mitochondria. Previous studies have largely focused on reconstructing the last common ancestor of all contemporary mitochondria (proto-mitochondria), but not on the more informative pre-mitochondria (the last common ancestor of mitochondria and their alphaproteobacterial sister clade). Using a phylogenomic approach and leveraging on the increased taxonomic sampling of alphaproteobacterial and eukaryotic genomes, we reconstructed the metabolisms of both proto-mitochondria and pre-mitochondria. Our reconstruction depicts a more streamlined proto-mitochondrion than these predicted by previous studies, and revealed several novel insights into the mitochondria-derived eukaryotic metabolisms including the lipid metabolism. Most strikingly, pre-mitochondrion was predicted to possess a plastid/parasite type of ATP/ADP translocase that imports ATP from the host, which posits pre-mitochondrion as an energy parasite that directly contrasts with the current role of mitochondria as the cell's energy producer. In addition, pre-mitochondrion was predicted to encode a large number of flagellar genes and several cytochrome oxidases functioning under low oxygen level, strongly supporting the previous finding that the mitochondrial ancestor was likely motile and capable of oxidative phosphorylation under microoxic condition.

  3. Autologous Germline Mitochondrial Energy Transfer (AUGMENT) in Human Assisted Reproduction.

    Science.gov (United States)

    Woods, Dori C; Tilly, Jonathan L

    2015-11-01

    Ovarian aging is characterized by a decline in both the total number and overall quality of oocytes, the latter of which has been experimentally tied to mitochondrial dysfunction. Clinical studies in the late 1990s demonstrated that transfer of cytoplasm aspirated from eggs of young female donors into eggs of infertile women at the time of intracytoplasmic sperm injection improved pregnancy success rates. However, donor mitochondria were identified in offspring, and the United States Food and Drug Administration raised questions about delivery of foreign genetic material into human eggs at the time of fertilization. Accordingly, heterologous cytoplasmic transfer, while promising, was in effect shut down as a clinical protocol. The recent discovery of adult oogonial (oocyte-generating) stem cells in mice, and subsequently in women, has since re-opened the prospects of delivering a rich source of pristine and patient-matched germline mitochondria to boost egg health and embryonic developmental potential without the need for young donor eggs to obtain cytoplasm. Herein we overview the science behind this new protocol, which has been patented and termed autologous germline mitochondrial energy transfer, and its use to date in clinical studies for improving pregnancy success in women with a prior history of assisted reproduction failure.

  4. Skeletal muscle mitochondrial H2O2 emission increases with immobilization and decreases after aerobic training in young and older men

    DEFF Research Database (Denmark)

    Gram, Martin; Vigelsø, Andreas; Yokota, Takashi;

    2015-01-01

    Mitochondrial dysfunction, defined as increased oxidative stress and lower capacity for energy production, may be seen with aging and may cause frailty, or it could be that it is secondary to physical inactivity. We studied the effect of two weeks of one-leg immobilization followed by six weeks...... two protocols pyruvate+malate (PM) and succinate+rotenone (SR). This allowed measurement of leak and ATP generating respiration from which the coupling efficiency can be calculated. Protein content of the antioxidants manganese superoxide dismuthase (MnSOD), CuZn-superoxide dismuthase (Cu...

  5. Cancer: Mitochondrial Origins.

    Science.gov (United States)

    Stefano, George B; Kream, Richard M

    2015-12-01

    The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial matrix. The intra-mitochondrial availability of molecular oxygen as the ultimate electron acceptor drives the evolutionary fashioned chemiosmotic production of ATP as a high-efficiency biological process. The mechanistic bases of carcinogenesis have demonstrated profound alteration of normative mitochondrial function, notably dysregulated respiratory processes. Accordingly, the classic Warburg effect functionally links aerobic glycolysis, aberrant production and release of lactate, and metabolic down-regulation of mitochondrial oxidative processes with the carcinogenetic phenotype. We surmise, however, that aerobic fermentation by cancer cells may also represent a developmental re-emergence of an evolutionarily conserved early phenotype, which was "sidelined" with the emergence of mitochondrial oxidative phosphorylation as a primary mechanism for ATP production in normal cells. Regardless of state-dependent physiological status in mixed populations of cancer cells, it has been established that mitochondria are functionally linked to the initiation of cancer and its progression. Biochemical, molecular, and physiological differences in cancer cell mitochondria, notably mtDNA heteroplasmy and allele-specific expression of selected nuclear genes, may represent major focal points for novel targeting and elimination of cancer cells in metastatic disease afflicting human populations. To date, and despite considerable research efforts, the practical realization of advanced mitochondrial

  6. Effects of acclimation temperature and cadmium exposure on cellular energy budgets in the marine mollusk Crassostrea virginica: linking cellular and mitochondrial responses.

    Science.gov (United States)

    Cherkasov, Anton S; Biswas, Pradip K; Ridings, Daisy M; Ringwood, Amy H; Sokolova, Inna M

    2006-04-01

    In order to understand the role of metabolic regulation in environmental stress tolerance, a comprehensive analysis of demand-side effects (i.e. changes in energy demands for basal maintenance) and supply-side effects (i.e. metabolic capacity to provide ATP to cover the energy demand) of environmental stressors is required. We have studied the effects of temperature (12, 20 and 28 degrees C) and exposure to a trace metal, cadmium (50 microg l(-1)), on the cellular energy budget of a model marine poikilotherm, Crassostrea virginica (eastern oysters), using oxygen demand for ATP turnover, protein synthesis, mitochondrial proton leak and non-mitochondrial respiration in isolated gill and hepatopancreas cells as demand-side endpoints and mitochondrial oxidation capacity, abundance and fractional volume as supply-side endpoints. Cadmium exposure and high acclimation temperatures resulted in a strong increase of oxygen demand in gill and hepatopancreas cells of oysters. Cd-induced increases in cellular energy demand were significant at 12 and 20 degrees C but not at 28 degrees C, possibly indicating a metabolic capacity limitation at the highest temperature. Elevated cellular demand in cells from Cd-exposed oysters was associated with a 2-6-fold increase in protein synthesis and, at cold acclimation temperatures, with a 1.5-fold elevated mitochondrial proton leak. Cellular aerobic capacity, as indicated by mitochondrial oxidation capacity, abundance and volume, did not increase in parallel to compensate for the elevated energy demand. Mitochondrial oxidation capacity was reduced in 28 degrees C-acclimated oysters, and mitochondrial abundance decreased in Cd-exposed oysters, with a stronger decrease (by 20-24%) in warm-acclimated oysters compared with cold-acclimated ones (by 8-13%). These data provide a mechanistic basis for synergism between temperature and cadmium stress on metabolism of marine poikilotherms. Exposure to combined temperature and cadmium stress may

  7. Teaching the Role of Mitochondrial Transport in Energy Metabolism

    Science.gov (United States)

    Passarella, Salvatore; Atlante, Anna

    2007-01-01

    Studies from our laboratories over recent years have uncovered the existence, and established the properties of a variety of mitochondrial transporters. The properties of these transporters throw light on a variety of biochemical phenomena that were previously poorly understood. In particular the role of mitochondrial transport in energy…

  8. Aerobic fitness level does not modulate changes in whole-body protein turnover produced by unaccustomed increases in energy expenditure

    Science.gov (United States)

    The effects of a sudden increase in energy expenditure (EE) on whole-body protein turnover vary between studies, and the possibility that fitness level modulates those responses has not been fully investigated. We hypothesized that aerobically trained individuals may exhibit adaptations that protec...

  9. Energy Flux, Lactate Shuttling, Mitochondrial Dynamics, and Hypoxia.

    Science.gov (United States)

    Brooks, George A

    2016-01-01

    Our understanding of what happens in working muscle and at the whole-body level at sea level and at high altitude is different from that a few years ago. If dietary CHO and nutrition are adequate, at sea level metabolism shifts from a mix of lipid and CHO-derived fuels toward carbohydrate (glycogen, glucose, and lactate) oxidation at moderate and greater exercise intensities. As given by the Crossover Concept, a percentage to total energy expenditure, lipid oxidation is greatest at exercise power outputs eliciting 45-50 % of VO2max with greater intensities requiring relatively more CHO and lesser lipid oxidation. At altitude, a given exercise power output is achieved at a greater relative intensity expressed as % VO2max. Hence, exercise under conditions of hypoxia requires greater glycolytic flux, and lactate production than does the same effort at sea level, normoxic conditions. Glycolytic flux is further augmented at altitude by the effect of hypoxemia on sympathetic nervous system activity. Hence, augmented lactate production during exercise is adaptive. Over the short term, accelerated lactate flux provides ATP supporting muscle contraction and balances cytosolic redox. As well, lactate provides and energy substrate and gluconeogenic precursor. Over a longer term, via redox and ROS-generating mechanisms, lactate may affect adaptations in mitochondrial biogenesis and solute (glucose and lactate) transport. While important, the energy substrate, gluconeogenic, and signaling qualities of lactate production and disposal at altitude need to be considered within the context of overall dietary energy intake and expenditure during exercise at sea level and high altitude. PMID:27343113

  10. MOLECULAR NEUROGENETICS OF MITOCHONDRIAL DISEASES

    Directory of Open Access Journals (Sweden)

    E. Cardaioli

    2012-01-01

    Full Text Available Mitochondrial diseases are an expanding group of clinically heterogeneous disorders associated with mitochondrial DNA (mtDNA mutations or nuclear gene defects. Whatever the mechanism, the final common step in mitochondrial disorders is a defect of energy production resulting from respiratory chain impairment. The complexity of the biochemical and genetic features of the respiratory chain accounts for the extraordinarily wide range of clinical presentations of mitochondrial disorders. In general, organs with high aerobic demand, such as skeletal muscle, brain and heart, are the most affected. However, virtually any organ or tissue in the body may be affected and the disorders can be multisystemic (mitochondrial encephalomyopathiesor confined to a single tissue. Moreover, mitochondrial diseases can be sporadic or transmitted by mendelian (nuclear genes or maternal inheritance (mutations in mtDNA. Precise diagnosis is often a challenge; we go through the traditional steps of the diagnostic process, starting with study of inheritance in the family, clinical manifestations in the individual,electrophysiology and imaging techniques at organ level, down to biochemistry, pathology and molecular genetics at tissue, cell and DNA level, respectively. In fact the ultimate goal is to reach, whenever possible, a definitive molecular diagnosis, which can permit rational therapeutic approach and a genetic counseling.

  11. Performance evaluation of an anaerobic/aerobic landfill-based digester using yard waste for energy and compost production.

    Science.gov (United States)

    Yazdani, Ramin; Barlaz, Morton A; Augenstein, Don; Kayhanian, Masoud; Tchobanoglous, George

    2012-05-01

    The objective of this study was to evaluate a new alternative for yard waste management by constructing, operating and monitoring a landfill-based two-stage batch digester (anaerobic/aerobic) with the recovery of energy and compost. The system was initially operated under anaerobic conditions for 366 days, after which the yard waste was aerated for an additional 191 days. Off gas generated from the aerobic stage was treated by biofilters. Net energy recovery was 84.3MWh, or 46kWh per million metric tons of wet waste (as received), and the biochemical methane potential of the treated waste decreased by 83% during the two-stage operation. The average removal efficiencies of volatile organic compounds and non-methane organic compounds in the biofilters were 96-99% and 68-99%, respectively.

  12. Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs.

    Science.gov (United States)

    Hsu, Chia-Chi; Wu, Ling-Chia; Hsia, Cheng-Yuan; Yin, Pen-Hui; Chi, Chin-Wen; Yeh, Tien-Shun; Lee, Hsin-Chen

    2015-09-01

    Human hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide particularly in Asia. Deregulation of cellular energetics was recently included as one of the cancer hallmarks. Compounds that target the mitochondria in cancer cells were proposed to have therapeutic potential. Biguanide drugs which inhibit mitochondrial complex I and repress mTOR signaling are clinically used to treat type 2 diabetes mellitus patients (T2DM) and were recently found to reduce the risk of HCC in T2DM patients. However, whether alteration of energy metabolism is involved in regulating the sensitivity of HCC to biguanide drugs is still unclear. In the present study, we treated four HCC cell lines with mitochondrial inhibitors (rotenone and oligomycin) and biguanide drugs (metformin and phenformin), and found that the HCC cells which had a higher mitochondrial respiration rate were more sensitive to these treatments; whereas the HCC cells which exhibited higher glycolysis were more resistant. When glucose was replaced by galactose in the medium, the altered energy metabolism from glycolysis to mitochondrial respiration in the HCC cells enhanced the cellular sensitivity to mitochondrial inhibitors and biguanides. The energy metabolism change enhanced AMP-activated protein kinase (AMPK) activation, mTOR repression and downregulation of cyclin D1 and Mcl-1 in response to the mitochondrial inhibitors and biguanides. In conclusion, our results suggest that increased mitochondrial oxidative metabolism upregulates the sensitivity of HCC to biguanide drugs. Enhancing the mitochondrial oxidative metabolism in combination with biguanide drugs may be a therapeutic strategy for HCC.

  13. Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kayo [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Hartman, Philip S. [Biology Department, Texas Christian University, Fort Worth, TX 76129 (United States); Ishii, Takamasa [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Suda, Hitoshi [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Akatsuka, Akira [Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Shoyama, Tetsuji [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Miyazawa, Masaki [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Ishii, Naoaki, E-mail: nishii@is.icc.u-tokai.ac.jp [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan)

    2011-01-21

    Research highlights: {yields} Growth and development of a fzo-1 mutant defective in the fusion process of mitochondria was delayed relative to the wild type of Caenorhabditis elegans. {yields} Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. {yields} fzo-1 animals had significantly lower metabolism than did N2 and mev-1 overproducing superoxide from mitochondrial electron transport complex II. {yields} Mitochondrial fusion can profoundly affect energy metabolism and development. -- Abstract: Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development.

  14. Effects of nitrosopropofol on mitochondrial energy-converting system.

    Science.gov (United States)

    Stevanato, Roberto; Momo, Federico; Marian, Michela; Rigobello, Maria Pia; Bindoli, Alberto; Bragadin, Marcantonio; Vincenti, Ezio; Scutari, Guido

    2002-10-01

    Nitrosopropofol (NOPR) is a relatively stable compound obtained from the reaction between the general anesthetic 2,6 diisopropylphenol (propofol) and nitrosoglutathione (GSNO) and bearing a more acidic phenol group than propofol. It interfered with mitochondrial energetic metabolism in a concentration-dependent manner. Concentrations as high as 100 or 200 microM disrupted both oxidative phosphorylation and electron transport. Low concentrations of NOPR (50 microM) markedly slowed down the electron transport rate which was insensitive both to ADP and uncoupler stimulation and spontaneously gradually stopped. Consequently, both the transmembrane potential production and the ATP synthesis system were affected. In the presence of 10 or 20 microM NOPR, mitochondria respired but showed a worsening of the respiratory control and produced a transmembrane potential useful to respond to a phosphorylation pulse, but were not able to restore it. These results were consistent with ATP synthesis and swelling experiments. NOPR was effective at concentrations lower than those required by the combination of propofol and GSNO, suggesting that mitochondria might be able to catalyze the reaction between GSNO and propofol and that the resulting metabolite was more active on mitochondrial membrane structure than the parent compounds. Although the details of the process are yet unknown, the mechanism presented may be of potential relevance to rationalize the pathophysiological effects of propofol.

  15. Regulation of Aerobic Energy Metabolism in Podospora anserina by Two Paralogous Genes Encoding Structurally Different c-Subunits of ATP Synthase

    Science.gov (United States)

    Sellem, Carole H.; di Rago, Jean-Paul; Lasserre, Jean-Paul; Ackerman, Sharon H.; Sainsard-Chanet, Annie

    2016-01-01

    Most of the ATP in living cells is produced by an F-type ATP synthase. This enzyme uses the energy of a transmembrane electrochemical proton gradient to synthesize ATP from ADP and inorganic phosphate. Proton movements across the membrane domain (FO) of the ATP synthase drive the rotation of a ring of 8–15 c-subunits, which induces conformational changes in the catalytic part (F1) of the enzyme that ultimately promote ATP synthesis. Two paralogous nuclear genes, called Atp9-5 and Atp9-7, encode structurally different c-subunits in the filamentous fungus Podospora anserina. We have in this study identified differences in the expression pattern for the two genes that correlate with the mitotic activity of cells in vegetative mycelia: Atp9-7 is transcriptionally active in non-proliferating (stationary) cells while Atp9-5 is expressed in the cells at the extremity (apex) of filaments that divide and are responsible for mycelium growth. When active, the Atp9-5 gene sustains a much higher rate of c-subunit synthesis than Atp9-7. We further show that the ATP9-7 and ATP9-5 proteins have antagonist effects on the longevity of P. anserina. Finally, we provide evidence that the ATP9-5 protein sustains a higher rate of mitochondrial ATP synthesis and yield in ATP molecules per electron transferred to oxygen than the c-subunit encoded by Atp9-7. These findings reveal that the c-subunit genes play a key role in the modulation of ATP synthase production and activity along the life cycle of P. anserina. Such a degree of sophistication for regulating aerobic energy metabolism has not been described before. PMID:27442014

  16. Performance evaluation of an anaerobic/aerobic landfill-based digester using yard waste for energy and compost production

    International Nuclear Information System (INIS)

    Highlights: ► Biochemical methane potential decreased by 83% during the two-stage operation. ► Net energy produced was 84.3 MWh or 46 kWh per million metric tons (Mg). ► The average removal efficiency of volatile organic compounds (VOCs) was 96–99%. ► The average removal efficiency of non-methane organic compounds (NMOCs) was 68–99%. ► The two-stage batch digester proved to be simple to operate and cost-effective. - Abstract: The objective of this study was to evaluate a new alternative for yard waste management by constructing, operating and monitoring a landfill-based two-stage batch digester (anaerobic/aerobic) with the recovery of energy and compost. The system was initially operated under anaerobic conditions for 366 days, after which the yard waste was aerated for an additional 191 days. Off gas generated from the aerobic stage was treated by biofilters. Net energy recovery was 84.3 MWh, or 46 kWh per million metric tons of wet waste (as received), and the biochemical methane potential of the treated waste decreased by 83% during the two-stage operation. The average removal efficiencies of volatile organic compounds and non-methane organic compounds in the biofilters were 96–99% and 68–99%, respectively.

  17. Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets

    DEFF Research Database (Denmark)

    Nielsen, Troels Halfeld; Olsen, N.V.; Toft, P;

    2013-01-01

    variables related to energy metabolism. METHODS: Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2 ) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis...... metabolism and degradation of cellular membranes, respectively. CONCLUSION: Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2 . The condition is biochemically characterised by a marked increase in cerebral lactate...... with a normal or elevated pyruvate level. The metabolic pattern is different from cerebral ischemia, which is characterised by simultaneous decreases in intracerebral pyruvate and PbtO2 . The study supports the hypothesis that cerebral ischemia and mitochondrial dysfunction may be identified and separated...

  18. Progress in drug development for Alzheimer's disease: An overview in relation to mitochondrial energy metabolism.

    Science.gov (United States)

    Hroudová, Jana; Singh, Namrata; Fišar, Zdeněk; Ghosh, Kallol K

    2016-10-01

    Current possibilities of Alzheimer's disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiological pathways and can act as inhibitors of cholinesterases (AChE, BuChE), inhibitors of monoamine oxidases (MAO-A, MAO-B), modulators of mitochondrial permeability transition pores, modulators of amyloid-beta binding alcohol dehydrogenase and antioxidants. Effects of clinically used as well as newly developed AD drugs were studied in relation to energy metabolism and mitochondrial functions, including oxidative phosphorylation, activities of enzymes of citric acid cycle or electron transfer system, mitochondrial membrane potential, calcium homeostasis, production of reactive oxygen species and MAO activity. PMID:27094132

  19. Translational Targeted Proteomics Profiling of Mitochondrial Energy Metabolic Pathways in Mouse and Human Samples.

    Science.gov (United States)

    Wolters, Justina C; Ciapaite, Jolita; van Eunen, Karen; Niezen-Koning, Klary E; Matton, Alix; Porte, Robert J; Horvatovich, Peter; Bakker, Barbara M; Bischoff, Rainer; Permentier, Hjalmar P

    2016-09-01

    Absolute measurements of protein abundance are important in the understanding of biological processes and the precise computational modeling of biological pathways. We developed targeted LC-MS/MS assays in the selected reaction monitoring (SRM) mode to quantify over 50 mitochondrial proteins in a single run. The targeted proteins cover the tricarboxylic acid cycle, fatty acid β-oxidation, oxidative phosphorylation, and the detoxification of reactive oxygen species. Assays used isotopically labeled concatemers as internal standards designed to target murine mitochondrial proteins and their human orthologues. Most assays were also suitable to quantify the corresponding protein orthologues in rats. After exclusion of peptides that did not pass the selection criteria, we arrived at SRM assays for 55 mouse, 52 human, and 51 rat proteins. These assays were optimized in isolated mitochondrial fractions from mouse and rat liver and cultured human fibroblasts and in total liver extracts from mouse, rat, and human. The developed proteomics approach is suitable for the quantification of proteins in the mitochondrial energy metabolic pathways in mice, rats, and humans as a basis for translational research. Initial data show that the assays have great potential for elucidating the adaptive response of human patients to mutations in mitochondrial proteins in a clinical setting.

  20. Nitric Oxide is Required for Homeostasis of Oxygen and Reactive Oxygen Species in Barley Roots under Aerobic Conditions

    DEFF Research Database (Denmark)

    Gupta, Kapuganti J; Hebelstrup, Kim; Kruger, Nicholas J;

    2014-01-01

    ), but the extent to which NO might also play a role in the energy metabolism of roots under normal aerobic conditions is unknown. Mitochondria, whose functions are central to aerobic metabolism, are the major source of NO in plants, and potential targets for NO include cytochrome c oxidase in the mitochondrial......Oxygen, the terminal electron acceptor for mitochondrial electron transport, is vital for plants because of its role in the production of ATP by oxidative phosphorylation. While photosynthetic oxygen production contributes to the oxygen supply in leaves, reducing the risk of oxygen limitation...... of mitochondrial metabolism under most conditions, root tissues often suffer oxygen deprivation during normal development due to the lack of an endogenous supply and isolation from atmospheric oxygen. Since changes in oxygen concentration have multiple effects on metabolism and energy production (Geigenberger...

  1. Compromised mitochondrial fatty acid synthesis in transgenic mice results in defective protein lipoylation and energy disequilibrium.

    Directory of Open Access Journals (Sweden)

    Stuart Smith

    Full Text Available A mouse model with compromised mitochondrial fatty acid synthesis has been engineered in order to assess the role of this pathway in mitochondrial function and overall health. Reduction in the expression of mitochondrial malonyl CoA-acyl carrier protein transacylase, a key enzyme in the pathway encoded by the nuclear Mcat gene, was achieved to varying extents in all examined tissues employing tamoxifen-inducible Cre-lox technology. Although affected mice consumed more food than control animals, they failed to gain weight, were less physically active, suffered from loss of white adipose tissue, reduced muscle strength, kyphosis, alopecia, hypothermia and shortened lifespan. The Mcat-deficient phenotype is attributed primarily to reduced synthesis, in several tissues, of the octanoyl precursors required for the posttranslational lipoylation of pyruvate and α-ketoglutarate dehydrogenase complexes, resulting in diminished capacity of the citric acid cycle and disruption of energy metabolism. The presence of an alternative lipoylation pathway that utilizes exogenous free lipoate appears restricted to liver and alone is insufficient for preservation of normal energy metabolism. Thus, de novo synthesis of precursors for the protein lipoylation pathway plays a vital role in maintenance of mitochondrial function and overall vigor.

  2. Twelve weeks of moderate aerobic exercise without dietary intervention or weight loss does not affect 24-h energy expenditure in lean and obese adolescents.

    Science.gov (United States)

    Exercise might have a persistent effect on energy expenditure and fat oxidation, resulting in increased fat loss. However, even without weight loss, exercise results in positive metabolic effects. The effect of an aerobic exercise program on 24-h total energy expenditure (TEE), and its components-ba...

  3. Twelve weeks of moderate aerobic exercise without dietary intervention or weight loss does not affect 24-h energy expenditure in lean and obese adolescents

    NARCIS (Netherlands)

    van der Heijden, Gert-Jan; Sauer, Pieter J. J.; Sunehag, Agneta L.

    2010-01-01

    Background: Exercise might have a persistent effect on energy expenditure and fat oxidation, resulting in increased fat loss. However, even without weight loss, exercise results in positive metabolic effects. The effect of an aerobic exercise program on 24-h total energy expenditure (TEE) and its co

  4. Mitochondrial cytopathies.

    Science.gov (United States)

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-09-01

    Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Most of mitochondrial proteins are encoded by the nuclear DNA (nDNA) whereas a very small fraction is encoded by the mitochondrial DNA (mtDNA). Mutations in mtDNA or mitochondria-related nDNA genes can result in mitochondrial dysfunction which leads to a wide range of cellular perturbations including aberrant calcium homeostasis, excessive reactive oxygen species production, dysregulated apoptosis, and insufficient energy generation to meet the needs of various organs, particularly those with high energy demand. Impaired mitochondrial function in various tissues and organs results in the multi-organ manifestations of mitochondrial diseases including epilepsy, intellectual disability, skeletal and cardiac myopathies, hepatopathies, endocrinopathies, and nephropathies. Defects in nDNA genes can be inherited in an autosomal or X-linked manners, whereas, mtDNA is maternally inherited. Mitochondrial diseases can result from mutations of nDNA genes encoding subunits of the electron transport chain complexes or their assembly factors, proteins associated with the mitochondrial import or networking, mitochondrial translation factors, or proteins involved in mtDNA maintenance. MtDNA defects can be either point mutations or rearrangements. The diagnosis of mitochondrial disorders can be challenging in many cases and is based on clinical recognition, biochemical screening, histopathological studies, functional studies, and molecular genetic testing. Currently, there are no satisfactory therapies available for mitochondrial disorders that significantly alter the course of the disease. Therapeutic options include symptomatic treatment, cofactor supplementation, and exercise. PMID:26996063

  5. Tongluo Xingnao Effervescent Tablet preserves mitochondrial energy metabolism and attenuates cognition deficits in APPswe/PS1De9 mice.

    Science.gov (United States)

    Dai, Yuan; Ma, Tao; Ren, Xiangyi; Wei, Jiangping; Fu, Wenjun; Ma, Yuntong; Xu, Shijun; Zhang, Zhanjun

    2016-09-01

    Tongluo Xingnao Effervescent Tablet (TXET), a traditional Chinese herbal formula composed of Ligusticum chuanxiong hor, Scutellaria baicalensis Georgi and Angelica sinensis, has been widely used to treat Alzheimer's disease (AD) and related dementias for decades in China. In the present study, we investigated the effects of TXET on mitochondrial function, energy metabolism and cognitive amelioration in the APPswe/PS1De9 transgenetic mouse model of AD. The energy charge and phosphocreatine, activity of the mitochondrial electron transport chain complexes, mitochondrial membrane potential, activity of Na(+)-K(+) ATPase and the expression levels of Bcl-2 and Bax in the brains were measured, respectively. TXET exhibits significant protection on mitochondrial function and energy supply in addition to ameliorating cognitive decline in APPswe/PS1De9 mice. TXET rescues mitochondrial function by increasing the mitochondrial membrane potential, energy charge levels, activity of respiratory chain complexes and Na(+)-K(+) ATPase activity. These findings suggest that TXET may attenuate cognition impairment through the restoration of mitochondrial function and energy metabolism in the brains in APPswe/PS1De9 mice. PMID:27461792

  6. Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis.

    Science.gov (United States)

    Shiraishi, J; Tatsumi, T; Keira, N; Akashi, K; Mano, A; Yamanaka, S; Matoba, S; Asayama, J; Yaoi, T; Fushiki, S; Fliss, H; Nakagawa, M

    2001-10-01

    Recent studies have suggested that apoptosis and necrosis share common features in their signaling pathway and that apoptosis requires intracellular ATP for its mitochondrial/apoptotic protease-activating factor-1 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal rat cardiac myocytes were first incubated for 1 h in glucose-free medium containing oligomycin to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing staurosporine and graded concentrations of glucose to manipulate intracellular ATP levels. Under ATP-depleting conditions, the cell death caused by staurosporine was primarily necrotic, as determined by creatine kinase release and nuclear staining with ethidium homodimer-1. However, under ATP-replenishing conditions, staurosporine increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. Caspase-3 activation by staurosporine was also ATP dependent. However, loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bax translocation, and cytochrome c release were observed in both apoptotic and necrotic cells. Moreover, cyclosporin A, an inhibitor of mitochondrial permeability transition, attenuated staurosporine-induced apoptosis and necrosis through the inhibition of DeltaPsi(m) reduction, cytochrome c release, and caspase-3 activation. Our data therefore suggest that staurosporine induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular ATP favors a shift from necrosis to apoptosis through caspase activation. PMID:11557554

  7. Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance

    DEFF Research Database (Denmark)

    Vollaard, Niels B J; Constantin-Teodosiu, Dimitru; Fredriksson, Katarina;

    2009-01-01

    It has not been established which physiological processes contribute to endurance training-related changes (Delta) in aerobic performance. For example, the relationship between intramuscular metabolic responses at the intensity used during training and improved human functional capacity has...... supervised cycling training (45 min at 70% of pretraining Vo(2max)) 4 times/wk for 6 wk. Performance was determined using a 15-min cycling time trial, and muscle biopsies were taken before and after a 10-min cycle at 70% of pretraining Vo(2max) to quantify substrate metabolism. Substantial interindividual...

  8. Mitochondrial reactive oxygen species modulate mosquito susceptibility to Plasmodium infection.

    Directory of Open Access Journals (Sweden)

    Renata L S Gonçalves

    Full Text Available BACKGROUND: Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS that modulate redox metabolism. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1, is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. CONCLUSION: We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection.

  9. Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection

    Science.gov (United States)

    Oliveira, Giselle A.; Andersen, John F.; Oliveira, Marcus F.; Oliveira, Pedro L.; Barillas-Mury, Carolina

    2012-01-01

    Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. Conclusion We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection. PMID:22815925

  10. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes.

    Science.gov (United States)

    Liu, Cong; Sekine, Shuichi; Ito, Kousei

    2016-07-01

    Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. PMID:27095095

  11. Aerobic Capacity, Activity Levels and Daily Energy Expenditure in Male and Female Adolescents of the Kenyan Nandi Sub-Group.

    Directory of Open Access Journals (Sweden)

    Alexander R Gibson

    Full Text Available The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years and 15 habitually active female (13.9±1.2 adolescents from a rural Nandi primary school are assessed. Aerobic capacity ([Formula: see text] was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The [Formula: see text] of the male and female adolescents were 73.9±5.7 ml(. kg(-1. min(-1 and 61.5±6.3 ml(. kg(-1. min(-1, respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time, 244±56 min (30%, 75±18 min (9% and 82±30 min (10%. Average total daily distance travelled to and from school was 7.5±3.0 km (0.8-13.4 km. Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ(. day(-1, 5.4±3.0 MJ(. day(-1 and 2.2±0.6. 70.6% of the variation in [Formula: see text] was explained by sex (partial R(2 = 54.7% and body mass index (partial R(2 = 15.9%. Energy expenditure and physical activity variables did not predict variation in [Formula: see text] once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success.

  12. Carotenoid charge transfer states and their role in energy transfer processes in LH1-RC complexes from aerobic anoxygenic phototrophs.

    Science.gov (United States)

    Šlouf, Václav; Fuciman, Marcel; Dulebo, Alexander; Kaftan, David; Koblížek, Michal; Frank, Harry A; Polívka, Tomáš

    2013-09-26

    Light-harvesting complexes ensure necessary flow of excitation energy into photosynthetic reaction centers. In the present work, transient absorption measurements were performed on LH1-RC complexes isolated from two aerobic anoxygenic phototrophs (AAPs), Roseobacter sp. COL2P containing the carotenoid spheroidenone, and Erythrobacter sp. NAP1 which contains the carotenoids zeaxanthin and bacteriorubixanthinal. We show that the spectroscopic data from the LH1-RC complex of Roseobacter sp. COL2P are very similar to those previously reported for Rhodobacter sphaeroides, including the transient absorption spectrum originating from the intramolecular charge-transfer (ICT) state of spheroidenone. Although the ICT state is also populated in LH1-RC complexes of Erythrobacter sp. NAP1, its appearance is probably related to the polarity of the bacteriorubixanthinal environment rather than to the specific configuration of the carotenoid, which we hypothesize is responsible for populating the ICT state of spheroidenone in LH1-RC of Roseobacter sp. COL2P. The population of the ICT state enables efficient S1/ICT-to-bacteriochlorophyll (BChl) energy transfer which would otherwise be largely inhibited for spheroidenone and bacteriorubixanthinal due to their low energy S1 states. In addition, the triplet states of these carotenoids appear well-tuned for efficient quenching of singlet oxygen or BChl-a triplets, which is of vital importance for oxygen-dependent organisms such as AAPs. PMID:23130956

  13. Physiological performance of warm-adapted marine ectotherms: Thermal limits of mitochondrial energy transduction efficiency.

    Science.gov (United States)

    Martinez, Eloy; Hendricks, Eric; Menze, Michael A; Torres, Joseph J

    2016-01-01

    Thermal regimes in aquatic systems have profound implications for the physiology of ectotherms. In particular, the effect of elevated temperatures on mitochondrial energy transduction in tropical and subtropical teleosts may have profound consequences on organismal performance and population viability. Upper and lower whole-organism critical temperatures for teleosts suggest that subtropical and tropical species are not susceptible to the warming trends associated with climate change, but sub-lethal effects on energy transduction efficiency and population dynamics remain unclear. The goal of the present study was to compare the thermal sensitivity of processes associated with mitochondrial energy transduction in liver mitochondria from the striped mojarra (Eugerres plumieri), the whitemouth croaker (Micropogonias furnieri) and the palometa (Trachinotus goodei), to those of the subtropical pinfish (Lagodon rhomboides) and the blue runner (Caranx crysos). Mitochondrial function was assayed at temperatures ranging from 10 to 40°C and results obtained for both tropical and subtropical species showed a reduction in the energy transduction efficiency of the oxidative phosphorylation (OXPHOS) system in most species studied at temperatures below whole-organism critical temperature thresholds. Our results show a loss of coupling between O2 consumption and ATP production before the onset of the critical thermal maxima, indicating that elevated temperature may severely impact the yield of ATP production per carbon unit oxidized. As warming trends are projected for tropical regions, increasing water temperatures in tropical estuaries and coral reefs could impact long-term growth and reproductive performance in tropical organisms, which are already close to their upper thermal limit.

  14. On the origin of 3-methylglutaconic acid in disorders of mitochondrial energy metabolism.

    Science.gov (United States)

    Ikon, Nikita; Ryan, Robert O

    2016-09-01

    3-methylglutaconic acid (3MGA)-uria occurs in numerous inborn errors of metabolism (IEM) associated with compromised mitochondrial energy metabolism. This organic acid arises from thioester cleavage of 3-methylglutaconyl CoA (3MG CoA), an intermediate in leucine catabolism. In individuals harboring mutations in 3MG CoA hydratase (i.e., primary 3MGA-uria), dietary leucine is the source of 3MGA. In secondary 3MGA-uria, however, no leucine metabolism defects have been reported. While others have suggested 3MGA arises from aberrant isoprenoid shunting from cytosol to mitochondria, an alternative route posits that 3MG CoA arises in three steps from mitochondrial acetyl CoA. Support for this biosynthetic route in IEMs is seen by its regulated occurrence in microorganisms. The fungus, Ustilago maydis, the myxobacterium, Myxococcus xanthus and the marine cyanobacterium, Lyngbya majuscule, generate 3MG CoA (or acyl carrier protein derivative) in the biosynthesis of iron chelating siderophores, iso-odd chain fatty acids and polyketide/nonribosomal peptide products, respectively. The existence of this biosynthetic machinery in these organisms supports a model wherein, under conditions of mitochondrial dysfunction, accumulation of acetyl CoA in the inner mitochondrial space as a result of inefficient fuel utilization drives de novo synthesis of 3MG CoA. Since humans lack the downstream biosynthetic capability of the organisms mentioned above, as 3MG CoA levels rise, thioester hydrolysis yields 3MGA, which is excreted in urine as unspent fuel. Understanding the metabolic origins of 3MGA may increase its utility as a biomarker. PMID:27091556

  15. Glycolytic Coupling to Mitochondrial Energy Production Ensures Survival in an Oxygen Rich Environment

    Science.gov (United States)

    Stefano, George B.; Kream, Richard M.

    2016-01-01

    The mitochondrion exhibits biochemical and functional variations that emerged by random chance as an evolutionary survival strategy, which include enhanced energy production driven by anaerobic respiratory mechanisms. In invertebrates, this mitochondrial anaerobic respiration permits survival at a lower energy state suited for this type of environment while yielding more ATP than by glycolysis alone. This ability provides a protective existential advantage in naturally occurring hypoxic environments via diminished free radical generation. In the blue mussel Mytilus edulis and other marine organisms, a functionally active mitochondrial anaerobic respiratory mechanism tailored to hypoxic conditions reflects an evolutionary adaptation/reworking of ancient metabolic pathways. Components of these pathways were also discovered and characterized as metabolic intermediates in plant parasites, specifically crown gall tumors. Mechanistic similarities between anaerobically functioning mitochondria in M. edulis and crown gall tissues and metabolic processes in human tumors are known to occur, demonstrating commonalities in diverse life energy processes. Furthermore, cytoplasmic glycolytic processes are now shown also to exhibit a dynamic capacity for enhanced energy generation by increasing its efficiency in hypoxic environments, making it equally dynamic in meeting its cellular survival goal. PMID:27439008

  16. Energetic and metabolic consequences of aerobic and an-aerobic ATP-production.

    NARCIS (Netherlands)

    Schreurs, V.V.A.M.; Aarts, M.J.; IJssennagger, N.; Hermans, J.; Hendriks, W.H.

    2007-01-01

    ATP, the currency of cellular energy metabolism, can be produced during aerobic and an-aerobic oxidation of metabolic substrates. The aerobic oxidation yields CO2 + H2O as metabolic end products while ATP is produced by oxidative phosphorylation in the mitochondria. Carbohydrate, protein and fat pro

  17. The role of the mitochondrial calcium uniporter in cerebral ischemia/reperfusion injury in rats involves regulation of mitochondrial energy metabolism.

    Science.gov (United States)

    Zhao, Qin; Wang, Shilei; Li, Yu; Wang, Peng; Li, Shuhong; Guo, Yunliang; Yao, Ruyong

    2013-04-01

    The mitochondrial calcium uniporter (MCU) maintains intracellular Ca2+ homeostasis by transporting Ca2+ from the cell cytosol into the mitochondrial matrix and is important for shaping Ca2+ signals and the activation of programmed cell death. Inhibition of MCU by ruthenium red (RR) or Ru360 has previously been reported to protect against neuronal death. The aim of the present study was to analyze the mechanisms underlying the effects of MCU activity in a rat model of cerebral ischemia/reperfusion (I/R) injury. Adult male Wistar rats were divided into 4 groups; sham, I/R, I/R + RR and I/R + spermine (Sper) and were subjected to reversible middle cerebral artery occlusion for 2 h followed by 24 h of reperfusion. A bolus injection of RR administered 30 min prior to ischemia was found to significantly decrease the total infarct volume and reduce neuronal damage and cell apoptosis compared with ischemia/reperfusion values. However, treatment with Sper, an activator of the MCU, increased the injury induced by I/R. Analysis of energy metabolism revealed that I/R induced progressive inhibition of complexes I‑IV of the electron transport chain, decreased ATP production, dissipated the mitochondrial membrane potential and increased the generation of reactive oxygen species. Treatment with RR ameliorated the condition, while spermine had the opposite effect. In conclusion, blocking MCU was demonstrated to exert protective effects against I/R injury and this process may be mediated by the prevention of energy failure.

  18. A Flavonoid Compound Promotes Neuronal Differentiation of Embryonic Stem Cells via PPAR-β Modulating Mitochondrial Energy Metabolism

    Science.gov (United States)

    Mei, Yu-qin; Pan, Zong-fu; Chen, Wen-teng; Xu, Min-hua; Zhu, Dan-yan; Yu, Yong-ping; Lou, Yi-jia

    2016-01-01

    Relatively little is known regarding mitochondrial metabolism in neuronal differentiation of embryonic stem (ES) cells. By using a small molecule, present research has investigated the pattern of cellular energy metabolism in neural progenitor cells derived from mouse ES cells. Flavonoid compound 4a faithfully facilitated ES cells to differentiate into neurons morphologically and functionally. The expression and localization of peroxisome proliferator-activated receptors (PPARs) were examined in neural progenitor cells. PPAR-β expression showed robust upregulation compared to solvent control. Treatment with PPAR-β agonist L165041 alone or together with compound 4a significantly promoted neuronal differentiation, while antagonist GSK0660 blocked the neurogenesis-promoting effect of compound 4a. Consistently, knockdown of PPAR-β in ES cells abolished compound 4a-induced neuronal differentiation. Interestingly, we found that mitochondrial fusion protein Mfn2 was also abolished by sh-PPAR-β, resulting in abnormal mitochondrial Ca2+ ([Ca2+]M) transients as well as impaired mitochondrial bioenergetics. In conclusion, we demonstrated that by modulating mitochondrial energy metabolism through Mfn2 and mitochondrial Ca2+, PPAR-β took an important role in neuronal differentiation induced by flavonoid compound 4a. PMID:27315062

  19. Lymphocytes Mitochondrial Physiology as Biomarker of Energy Metabolism during Fasted and Fed Conditions

    Directory of Open Access Journals (Sweden)

    Erika Cortez

    2012-01-01

    Full Text Available Mitochondria are central coordinators of energy metabolism, and changes of their physiology have long been associated with metabolic disorders. Thus, observations of energy dynamics in different cell types are of utmost importance. Therefore, tools with quick and easy handling are needed for consistent evaluations of such interventions. In this paper, our main hypothesis is that during different nutritional situations lymphocytes mitochondrial physiology could be associated with the metabolism of other cell types, such as cardiomyocytes, and consequently be used as metabolic biomarker. Blood lymphocytes and heart muscle fibers were obtained from both fed and 24 h-fasted mice, and mitochondrial analysis was assessed by high-resolution respirometry and western blotting. Carbohydrate-linked oxidation and fatty acid oxidation were significantly higher after fasting. Carnitine palmitoil transferase 1 and uncouple protein 2 contents were increased in the fasted group, while the glucose transporters 1 and 4 and the ratio phosphorylated AMP-activated protein kinase/AMPK did not change between groups. In summary, under a nutritional status modification, mitochondria demonstrated earlier adaptive capacity than other metabolic sensors such as glucose transporters and AMPK, suggesting the accuracy of mitochondria physiology of lymphocytes as biomarker for metabolic changes.

  20. Mitochondrial Function and Energy Metabolism in Umbilical Cord Blood- and Bone Marrow-Derived Mesenchymal Stem Cells

    Science.gov (United States)

    Palomäki, Sami; Lehtonen, Siri; Ritamo, Ilja; Valmu, Leena; Nystedt, Johanna; Laitinen, Saara; Leskelä, Hannnu-Ville; Sormunen, Raija; Pesälä, Juha; Nordström, Katrina; Vepsäläinen, Ari; Lehenkari, Petri

    2012-01-01

    Human mesenchymal stem cells (hMSCs) are an attractive choice for a variety of cellular therapies. hMSCs can be isolated from many different tissues and possess unique mitochondrial properties that can be used to determine their differentiation potential. Mitochondrial properties may possibly be used as a quality measure of hMSC-based products. Accordingly, the present work focuses on the mitochondrial function of hMSCs from umbilical cord blood (UCBMSC) cells and bone marrow cells from donors younger than 18 years of age (BMMSC 50). Changes of ultrastructure and energy metabolism during osteogenic differentiation in all hMSC types were studied in detail. Results show that despite similar surface antigen characteristics, the UCBMSCs had smaller cell surface area and possessed more abundant rough endoplasmic reticulum than BMMSC >50. BMMSC 50 and BMMSC 50 showed a lower level of mitochondrial maturation and differentiation capacity. UCBMSCs and BMMSCs also showed a different pattern of exocytosed proteins and glycoproteoglycansins. These results indicate that hMSCs with similar cell surface antigen expression have different mitochondrial and functional properties, suggesting different maturation levels and other significant biological variations of the hMSCs. Therefore, it appears that mitochondrial analysis presents useful characterization criteria for hMSCs intended for clinical use. PMID:21615273

  1. The effect of 6 days of sodium phosphate supplementation on appetite, energy intake, and aerobic capacity in trained men and women.

    Science.gov (United States)

    West, Jessica S; Ayton, Tom; Wallman, Karen E; Guelfi, Kym J

    2012-12-01

    Ingestion of an acute dose of phosphate has been shown to attenuate energy intake in the subsequent meal. This raises the question of whether the practice of phosphate supplementation over a number of days by athletes to enhance performance also influences energy intake. This study investigated the effect of 6 d of phosphate supplementation on appetite and energy intake, as well as aerobic capacity, in trained individuals. Twenty participants completed two 6-d phases of supplementation with either sodium phosphate (50 mg/kg of fat-free mass per day) or a placebo in a double-blinded, counterbalanced design. On Days 1, 2, and 6 of supplementation, a laboratory meal was provided to assess appetite and ad libitum energy intake. All other food and drink consumed during each supplementation phase were recorded in a food diary. After the 6 d of supplementation, peak aerobic capacity (VO(2peak)) was assessed. There was no difference in energy intake at the laboratory meal after an acute dose (i.e., on Day 1; placebo 2,471 ± 919 kJ, phosphate 2,353 ± 987 kJ; p = .385) or prolonged supplementation with sodium phosphate (p = .581) compared with placebo. Likewise, there was no difference in VO(2peak) with phosphate supplementation (placebo 52.6 ± 5.2 ml · kg(-1) · min(-1), phosphate 53.3 ± 6.1 ml · kg(-1) · min(-1); p = .483). In summary, 6 d of sodium phosphate supplementation does not appear to influence energy intake. Therefore, athletes supplementing with sodium phosphate can do so without hindering their nutritional status. However, given that phosphate supplementation failed to improve aerobic capacity, the ergogenic benefit of this supplement remains questionable.

  2. A review of the multi-level adaptations for maximizing aerobic dive duration in marine mammals: from biochemistry to behavior.

    Science.gov (United States)

    Davis, Randall W

    2014-01-01

    Marine mammals exhibit multi-level adaptations, from cellular biochemistry to behavior, that maximize aerobic dive duration. A dive response during aerobic dives enables the efficient use of blood and muscle oxygen stores, but it is exercise modulated to maximize the aerobic dive limit at different levels of exertion. Blood volume and concentrations of blood hemoglobin and muscle myoglobin are elevated and serve as a significant oxygen store that increases aerobic dive duration. However, myoglobin is not homogeneously distributed in the locomotory muscles and is highest in areas that produce greater force and consume more oxygen during aerobic swimming. Muscle fibers are primarily fast and slow twitch oxidative with elevated mitochondrial volume densities and enhanced oxidative enzyme activities that are highest in areas that produce more force generation. Most of the muscle mitochondria are interfibriller and homogeneously distributed. This reduces the diffusion distance between mitochondria and helps maintain aerobic metabolism under hypoxic conditions. Mitochondrial volume densities and oxidative enzyme activities are also elevated in certain organs such as liver, kidneys, and stomach. Hepatic and renal function along with digestion and assimilation continue during aerobic dives to maintain physiological homeostasis. Most ATP production comes from aerobic fat metabolism in carnivorous marine mammals. Glucose is derived mostly from gluconeogenesis and is conserved for tissues such as red blood cells and the central nervous system. Marine mammals minimize the energetic cost of swimming and diving through body streamlining, efficient, lift-based propulsive appendages, and cost-efficient modes of locomotion that reduce drag and take advantage of changes in buoyancy with depth. Most dives are within the animal's aerobic dive limit, which maximizes time underwater and minimizes recovery time at the surface. The result of these adaptations is increased breath

  3. Protein-protein interactions of mitochondrial-associated protein via bioluminescence resonance energy transfer

    Science.gov (United States)

    Koshiba, Takumi

    2015-01-01

    Protein-protein interactions are essential biological reactions occurring at inter- and intra-cellular levels. The analysis of their mechanism is generally required in order link to understand their various cellular functions. Bioluminescence resonance energy transfer (BRET), which is based on an enzymatic activity of luciferase, is a useful tool for investigating protein-protein interactions in live cells. The combination of the BRET system and biomolecular fluorescence complementation (BiFC) would provide us a better understanding of the hetero-oligomeric structural states of protein complexes. In this review, we discuss the application of BRET to the protein-protein interactions of mitochondrial-associated proteins and discuss its physiological relevance. PMID:27493852

  4. Comparison of Substrate Oxidation and Energy Expenditure During Acute Aerobic Exercise With Moderate and High Intensity in Patients With Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Rezaei Nasab

    2015-09-01

    Full Text Available Background Type 2 diabetes and obesity are related to other metabolic disorders such as insulin resistance, high blood pressure, visceral obesity increase and metabolic syndrome with high danger of cardiovascular disease expansion. Objectives This study aimed to determine whether in patients with type 2 diabetes, substrate oxidation and energy expenditure were affected by the type of intensity of acute aerobic exercise they were provided. Materials and Methods Nine men with type 2 diabetes (Mean ± SD; age 52.6 ± 0.36 years, Body Mass Index (BMI = 30.3 ± 2.4 and 9 obese control group (Mean ± SD; age 49.1 ± 1.4 years, BMI = 31.3 ± 1.8 were participated in this study. In the first session, anthropometric measurements, body composition and maximum oxygen uptake (VO2 peak were measured in all subjects. In the next sessions, subjects completed two acute aerobic exercises on separate days in a crossover design. The two exercise trials performed at intensity of 60% and 80% VO2 peak after fasting for at least 10 hours. Means of volume of oxygen (VO2 and Volume of Carbon dioxide (VCO2 were calculated during 30 minutes for measuring the rates of fat oxidation, carbohydrate oxidation and energy expenditure at each intensity. Results The results showed that substrate oxidation and energy expenditure were lower in the diabetic group (P < 0.05 compared to the control one. Also, the results revealed that carbohydrate oxidation and energy expenditure were statistically increased by providing high intensity rather than moderate intensity; however, fat oxidation was statistically increased by providing moderate intensity rather than high intensity (P < 0.05. Conclusions According to the results of the present study, aerobic exercise at moderate intensity and proper time can be considered as a special treatment to prevent diabetes complications and related disorders, particularly obesity.

  5. Aerobic exercise (image)

    Science.gov (United States)

    Aerobic exercise gets the heart working to pump blood through the heart more quickly and with more force than ... must be oxygenated more quickly, which quickens respiration. Aerobic exercise strengthens the heart and boosts healthy cholesterol ...

  6. Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.

    Science.gov (United States)

    Naia, Luana; Ferreira, I Luísa; Cunha-Oliveira, Teresa; Duarte, Ana I; Ribeiro, Márcio; Rosenstock, Tatiana R; Laço, Mário N; Ribeiro, Maria J; Oliveira, Catarina R; Saudou, Frédéric; Humbert, Sandrine; Rego, A Cristina

    2015-02-01

    Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (Δψm) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the Δψm in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.

  7. Impaired mitochondrial energy production and ABC transporter function-A crucial interconnection in dementing proteopathies of the brain.

    Science.gov (United States)

    Pahnke, Jens; Fröhlich, Christina; Krohn, Markus; Schumacher, Toni; Paarmann, Kristin

    2013-10-01

    Ageing is the main risk factor for the development of dementing neurodegenerative diseases (NDs) and it is accompanied by the accumulation of variations in mitochondrial DNA. The resulting tissue-specific alterations in ATP production and availability cause deteriorations of cerebral clearance mechanisms that are important for the removal of toxic peptides and its aggregates. ABC transporters were shown to be the most important exporter superfamily for toxic peptides, e.g. β-amyloid and α-synuclein. Their activity is highly dependent on the availability of ATP and forms a directed energy-exporter network, linking decreased mitochondrial function with highly impaired ABC transporter activity and disease progression. In this paper, we describe a network based on interactions between ageing, energy metabolism, regeneration, accumulation of toxic peptides and the development of proteopathies of the brain with a focus on Alzheimer's disease (AD). Additionally, we provide new experimental evidence for interactions within this network in regenerative processes in AD.

  8. Structure and function of the mitochondrial calcium uniporter complex.

    Science.gov (United States)

    De Stefani, Diego; Patron, Maria; Rizzuto, Rosario

    2015-09-01

    The mitochondrial calcium uniporter (MCU) is the critical protein of the inner mitochondrial membrane mediating the electrophoretic Ca²⁺ uptake into the matrix. It plays a fundamental role in the shaping of global calcium signaling and in the control of aerobic metabolism as well as apoptosis. Two features of mitochondrial calcium signaling have been known for a long time: i) mitochondrial Ca²⁺ uptake widely varies among cells and tissues, and ii) channel opening strongly relies on the extramitochondrial Ca²⁺ concentration, with low activity at resting [Ca²⁺] and high capacity as soon as calcium signaling is activated. Such complexity requires a specialized molecular machinery, with several primary components can be variably gathered together in order to match energy demands and protect from toxic stimuli. In line with this, MCU is now recognized to be part of a macromolecular complex known as the MCU complex. Our understanding of the structure and function of the MCU complex is now growing promptly, revealing an unexpected complexity that highlights the pleiotropic role of mitochondrial Ca²⁺ signals. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

  9. Exercise-induced mitochondrial biogenesis - with special reference to mitochondrial transcription factors and lipin-1

    OpenAIRE

    Wallman Appel, Susanna E

    2012-01-01

    Mitochondrial biogenesis is one prominent adaptation to endurance training in skeletal muscle tissue. An increased mitochondrial density of the muscle fibres contributes to an enhanced aerobic capacity and thereby to improved fatigueresistance. Multiple signalling pathways and transcriptional networks are involved in controlling mitochondrial biogenesis. The transcriptional co-regulator lipin-1 is one factor proposed to contribute, based on its ability to interact with PGC-1α a...

  10. Effect of short-term thyroxine administration on energy metabolism and mitochondrial efficiency in humans.

    Directory of Open Access Journals (Sweden)

    Darcy L Johannsen

    Full Text Available The physiologic effects of triiodothyronine (T3 on metabolic rate are well-documented; however, the effects of thyroxine (T4 are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux ((31P MRS and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059 without a change in resting ATP demand (i.e., ATP flux of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration and the coupled state of the mitochondria (RCR were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively. Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss.

  11. The assembly of mitochondrial complex I : a product of nuclear-mitochondrial synergy

    NARCIS (Netherlands)

    Vogel, Rutger Oscar

    2007-01-01

    Mitochondria are essential to cellular energy production. Embedded in the mitochondrial inner membrane, the engine of the mitochondrial powerhouse is formed by the five enzymatic complexes of the oxidative phosphorylation (OXPHOS) system. Dysfunction of this system results in mitochondrial disease,

  12. Energy transfer in an LH4-like light harvesting complex from the aerobic purple photosynthetic bacterium Roseobacter denitrificans

    Energy Technology Data Exchange (ETDEWEB)

    Niedzwiedzki, Dariusz; Fuciman, Marcel; Frank, Harry A; Blankenship, R. E.

    A peripheral light-harvesting complex from the aerobic purple bacterium Roseobacter (R.) denitrificans was purified and its photophysical properties characterized. The complex contains two types of pigments, bacteriochlorophyll (BChl) a and the carotenoid (Car) spheroidenone and possesses unique spectroscopic properties. It appears to lack the B850 bacteriochlorophyll a Q{sub y} band that is typical for similar light-harvesting complex 2 antennas. Circular dichroism and low temperature steady-state absorption spectroscopy revealed that the B850 band is present but is shifted significantly to shorter wavelengths and overlaps with the B800 band at room temperature. Such a spectral signature classifies this protein as a member of the light-harvesting complex 4 class of peripheral light-harvesting complexes, along with the previously known light-harvesting complex 4 from Rhodopseudomonas palustris. The influence of the spectral change on the light-harvesting ability was studied using steady-state absorption, fluorescence, circular dichroism, femtosecond and microsecond time-resolved absorption and time-resolved fluorescence spectroscopies. The results were compared to the properties of the similar (in pigment composition) light-harvesting complex 2 from aerobically grown Rhodobacter sphaeroides and are understood within the context of shared similarities and differences and the putative influence of the pigments on the protein structure and its properties.

  13. Mitochondrial Dynamics in Diabetes

    OpenAIRE

    Yoon, Yisang; Galloway, Chad A.; Jhun, Bong Sook; Yu, Tianzheng

    2011-01-01

    Mitochondria are at the center of cellular energy metabolism and regulate cell life and death. The cell biological aspect of mitochondria, especially mitochondrial dynamics, has drawn much attention through implications in human pathology, including neurological disorders and metabolic diseases. Mitochondrial fission and fusion are the main processes governing the morphological plasticity and are controlled by multiple factors, including mechanochemical enzymes and accessory proteins. Emergin...

  14. Primary clear cell renal carcinoma cells display minimal mitochondrial respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition by 3-Bromopyruvate.

    OpenAIRE

    Nilsson, Helén; Lindgren, David; Mandahl Forsberg, A; Mulder, Hindrik; Axelson, Håkan; Johansson, Martin

    2015-01-01

    Changes of cellular metabolism are an integral property of the malignant potential of most cancer cells. Already in the 1930s, Otto Warburg observed that tumor cells preferably utilize glycolysis and lactate fermentation for energy production, rather than the mitochondrial oxidative phosphorylation dominating in normal cells, a phenomenon today known as the Warburg effect. Even though many tumor types display a high degree of aerobic glycolysis, they still retain the activity of other energy-...

  15. HIV and Cocaine Impact Glial Metabolism: Energy Sensor AMP-activated protein kinase Role in Mitochondrial Biogenesis and Epigenetic Remodeling

    Science.gov (United States)

    Samikkannu, Thangavel; Atluri, Venkata S. R.; Nair, Madhavan P. N.

    2016-01-01

    HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS. However, the role of cocaine in accelerating HIV associated energy deficit and its impact on neuronal dysfunction has not been elucidated yet. The aim of this study is to elucidate the molecular mechanism of HIV associated neuropathogenesis in cocaine abuse and how it accelerates the energy sensor AMPKs and its subsequent effect on mitochondrial oxidative phosphorylation (OXPHOS), BRSKs, CDC25B/C, MAP/Tau, Wee1 and epigenetics remodeling complex SWI/SNF. Results showed that cocaine exposure during HIV infection significantly increased the level of p24, reactive oxygen species (ROS), ATP-utilization and upregulated energy sensor AMPKs, CDC25B/C, MAP/Tau and Wee1 protein expression. Increased ROS production subsequently inhibits OCR/ECAR ratio and OXPHOS, and eventually upregulate epigenetics remodeling complex SWI/SNF in CHME-5 cells. These results suggest that HIV infection induced energy deficit and metabolic dysfunction is accelerated by cocaine inducing energy sensor AMPKs, mitochondrial biogenesis and chromatin remodeling complex SWI/SNF activation, which may lead to neuroAIDS disease progression. PMID:27535703

  16. HIV and Cocaine Impact Glial Metabolism: Energy Sensor AMP-activated protein kinase Role in Mitochondrial Biogenesis and Epigenetic Remodeling.

    Science.gov (United States)

    Samikkannu, Thangavel; Atluri, Venkata S R; Nair, Madhavan P N

    2016-01-01

    HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS. However, the role of cocaine in accelerating HIV associated energy deficit and its impact on neuronal dysfunction has not been elucidated yet. The aim of this study is to elucidate the molecular mechanism of HIV associated neuropathogenesis in cocaine abuse and how it accelerates the energy sensor AMPKs and its subsequent effect on mitochondrial oxidative phosphorylation (OXPHOS), BRSKs, CDC25B/C, MAP/Tau, Wee1 and epigenetics remodeling complex SWI/SNF. Results showed that cocaine exposure during HIV infection significantly increased the level of p24, reactive oxygen species (ROS), ATP-utilization and upregulated energy sensor AMPKs, CDC25B/C, MAP/Tau and Wee1 protein expression. Increased ROS production subsequently inhibits OCR/ECAR ratio and OXPHOS, and eventually upregulate epigenetics remodeling complex SWI/SNF in CHME-5 cells. These results suggest that HIV infection induced energy deficit and metabolic dysfunction is accelerated by cocaine inducing energy sensor AMPKs, mitochondrial biogenesis and chromatin remodeling complex SWI/SNF activation, which may lead to neuroAIDS disease progression. PMID:27535703

  17. Energy, ageing, fidelity and sex: oocyte mitochondrial DNA as a protected genetic template.

    Science.gov (United States)

    de Paula, Wilson B M; Lucas, Cathy H; Agip, Ahmed-Noor A; Vizcay-Barrena, Gema; Allen, John F

    2013-07-19

    Oxidative phosphorylation couples ATP synthesis to respiratory electron transport. In eukaryotes, this coupling occurs in mitochondria, which carry DNA. Respiratory electron transport in the presence of molecular oxygen generates free radicals, reactive oxygen species (ROS), which are mutagenic. In animals, mutational damage to mitochondrial DNA therefore accumulates within the lifespan of the individual. Fertilization generally requires motility of one gamete, and motility requires ATP. It has been proposed that oxidative phosphorylation is nevertheless absent in the special case of quiescent, template mitochondria, that these remain sequestered in oocytes and female germ lines and that oocyte mitochondrial DNA is thus protected from damage, but evidence to support that view has hitherto been lacking. Here we show that female gametes of Aurelia aurita, the common jellyfish, do not transcribe mitochondrial DNA, lack electron transport, and produce no free radicals. In contrast, male gametes actively transcribe mitochondrial genes for respiratory chain components and produce ROS. Electron microscopy shows that this functional division of labour between sperm and egg is accompanied by contrasting mitochondrial morphology. We suggest that mitochondrial anisogamy underlies division of any animal species into two sexes with complementary roles in sexual reproduction. We predict that quiescent oocyte mitochondria contain DNA as an unexpressed template that avoids mutational accumulation by being transmitted through the female germ line. The active descendants of oocyte mitochondria perform oxidative phosphorylation in somatic cells and in male gametes of each new generation, and the mutations that they accumulated are not inherited. We propose that the avoidance of ROS-dependent mutation is the evolutionary pressure underlying maternal mitochondrial inheritance and the developmental origin of the female germ line. PMID:23754815

  18. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities.

  19. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities. PMID:26118693

  20. Mitochondrial Dysfunction and Psychiatric Disorders

    OpenAIRE

    Shaw-Hwa Jou; Nan-Yin Chiu; Chin-San Liu

    2009-01-01

    Mitochondria are intracellular organelles crucial in the production of cellular energy.Mitochondrial diseases may result from malfunctions in this biochemical cascade. Severalinvestigators have proposed that mitochondrial dysfunction is related to the pathophysiologyof bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). Theauthors reviewed recent study findings and tried to delineate the current understanding of thecorrelation between mitochondrial dysfunction and p...

  1. Physical Fitness and Mitochondrial Respiratory Capacity in Horse Skeletal Muscle

    OpenAIRE

    Votion, Dominique-Marie; Gnaiger, Erich; Lemieux, Hélène; Mouithys-Mickalad, Ange; Serteyn, Didier

    2012-01-01

    Background Within the animal kingdom, horses are among the most powerful aerobic athletic mammals. Determination of muscle respiratory capacity and control improves our knowledge of mitochondrial physiology in horses and high aerobic performance in general. Methodology/Principal Findings We applied high-resolution respirometry and multiple substrate-uncoupler-inhibitor titration protocols to study mitochondrial physiology in small (1.0–2.5 mg) permeabilized muscle fibres sampled from triceps ...

  2. [Exercise and aging: regulation of mitochondrial function and redox system].

    Science.gov (United States)

    Sun, Li-Juan; Zhang, Yong; Liu, Jian-Kang

    2014-10-01

    Evidence shows that aging is closely related to mitochondrial decay and redox imbalance. With aging, both mitochondrial content and protein synthesis declined and free radicals, the by-products of mitochondrial metabolism and their oxidation to lipids, proteins and nuclear acids increased. The age-related declines in mitochondrial function and redox imbalance affect physical function, induce insulin resistance and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, thus, play a major role in regulation of life span. Therefore, mitochondrion may be the most important determinant of life span. Increasing evidence demonstrates that long-term aerobic exercise could prevent age-related diseases and improve life quality of aged people. Exercise may possibly stimulate mitochondrial biogenesis and phase II antioxidant defense system to regulate mitochondrial function and balance of redox system. Therefore, regular aerobic exercise may prevent age-related diseases, increase life quality and prolong life span through regulation of mitochondrial function and redox balance. PMID:25764789

  3. Amino acid incorporation into the protein of mitochondrial preparations from cerebral cortex and spinal cord.

    Science.gov (United States)

    Bachelard, H S

    1966-07-01

    1. Washed guinea-pig cerebral-cortex mitochondria incorporate [(14)C]leucine into their protein at a rate comparable with the rates reported for liver or heart mitochondria only if the mitochondria are separated from myelin and nerve endings by density-gradient centrifugation. 2. The non-mitochondrial components (myelin and nerve endings) of brain mitochondrial preparations incorporated [(14)C]leucine at a negligible rate. 3. The mitochondria do not require an exogenous supply of energy or a full supply of amino acids to support the process. 4. The incorporation rate was linear up to 2hr. aerobic incubation at 30 degrees and was inhibited by chloramphenicol, only slightly by actinomycin D and not by penicillin or pretreatment with ribonuclease. The observed incorporation is considered to be unlikely to be due to contaminating cytoplasmic ribosomes or bacteria. 5. The process was also studied in mitochondrial preparations from rabbit cerebral cortex and spinal cord.

  4. Effects of ingesting JavaFit Energy Extreme functional coffee on aerobic and anaerobic fitness markers in recreationally-active coffee consumers

    OpenAIRE

    Kreider Richard B; Wilborn Colin D; Wismann Jennifer A; Taylor Lemuel W; Roberts Michael D; Willoughby Darryn S

    2007-01-01

    Abstract The purpose of this study was to examine the effects of ingesting JavaFit™ Energy Extreme (JEE) on aerobic and anaerobic performance measures in recreationally-active male and female coffee drinkers. Five male (27.6 ± 4.2 yrs, 93.2 ± 11.7 kg, 181.6 ± 6.9 cm) and five female (29 ± 4.6 yrs, 61.5 ± 9.2 kg, 167.6 ± 6.9 cm) regular coffee drinkers (i.e., 223.9 ± 62.7 mg·d-1 of caffeine) participated in this study. In a cross-over, randomized design, participants performed a baseline (BASE...

  5. MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India); Binukumar, B.K.; Gill, Kiran Dip [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012 (India); Flora, Swaran J.S., E-mail: sjsflora@hotmail.com [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India)

    2011-11-15

    Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

  6. Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice.

    Science.gov (United States)

    Stephenson, Erin J; Ragauskas, Alyse; Jaligama, Sridhar; Redd, JeAnna R; Parvathareddy, Jyothi; Peloquin, Matthew J; Saravia, Jordy; Han, Joan C; Cormier, Stephania A; Bridges, Dave

    2016-06-01

    We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle.

  7. Catabolic efficiency of aerobic glycolysis: The Warburg effect revisited

    Directory of Open Access Journals (Sweden)

    Zhou Yi

    2010-05-01

    Full Text Available Abstract Background Cancer cells simultaneously exhibit glycolysis with lactate secretion and mitochondrial respiration even in the presence of oxygen, a phenomenon known as the Warburg effect. The maintenance of this mixed metabolic phenotype is seemingly counterintuitive given that aerobic glycolysis is far less efficient in terms of ATP yield per moles of glucose than mitochondrial respiration. Results Here, we resolve this apparent contradiction by expanding the notion of metabolic efficiency. We study a reduced flux balance model of ATP production that is constrained by the glucose uptake capacity and by the solvent capacity of the cell's cytoplasm, the latter quantifying the maximum amount of macromolecules that can occupy the intracellular space. At low glucose uptake rates we find that mitochondrial respiration is indeed the most efficient pathway for ATP generation. Above a threshold glucose uptake rate, however, a gradual activation of aerobic glycolysis and slight decrease of mitochondrial respiration results in the highest rate of ATP production. Conclusions Our analyses indicate that the Warburg effect is a favorable catabolic state for all rapidly proliferating mammalian cells with high glucose uptake capacity. It arises because while aerobic glycolysis is less efficient than mitochondrial respiration in terms of ATP yield per glucose uptake, it is more efficient in terms of the required solvent capacity. These results may have direct relevance to chemotherapeutic strategies attempting to target cancer metabolism.

  8. Aerobic exercise in children with oxidative phosphorylation defects

    Directory of Open Access Journals (Sweden)

    Luuk Schreuder

    2010-03-01

    Full Text Available Fatigue and exercise intolerance are symptoms in children with metabolic myopathy. Frequently this is combined with muscle pain in children with mitochondrial myopathy. Offering therapeutic advice remains challenging in this patient group. Here we describe five children above the age of four years, with normal intelligence, myopathy, exercise intolerance, motor developmental delay, and fatigue, who were diagnosed with a mitochondrial dysfunction. Based on the positive experience of condition training in adults with mitochondrial disease and inactivity, aerobic exercise training was advised for all the children. Because of the lack of clear protocols for individualized mitochondrial myopathies, regular training was initiated. The Movement Assessment Battery of Children, the Jamar dynamometer for grip force, and the Bruce protocol treadmill test were applied for evaluation. No patient showed significant disease progression on a weekly scheme of strength training or on aerobic training during periods varying between 6 and 18 months. Only one out of the five patients has shown an improvement after a period of structured, aerobic training, demonstrating good compliance and motivation over the course of 18 months. Some patients developed severe muscle pain after explosive exercise. Even in a relatively homogenous, intelligent group of patients and motivated parents, we could not reach full compliance. With our case studies, we would like to draw attention to the importance and pitfalls of movement therapy in children with mitochondrial disease.

  9. Mitochondrial haplogroups

    DEFF Research Database (Denmark)

    Benn, Marianne; Schwartz, Marianne; Nordestgaard, Børge G;

    2008-01-01

    Rare mutations in the mitochondrial genome may cause disease. Mitochondrial haplogroups defined by common polymorphisms have been associated with risk of disease and longevity. We tested the hypothesis that common haplogroups predict risk of ischemic cardiovascular disease, morbidity from other...

  10. Mitochondrial Diseases

    Science.gov (United States)

    ... disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are ... cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how many mitochondria ...

  11. Performance of 14 full-scale sewage treatment plants: comparison between four aerobic technologies regarding effluent quality, sludge production and energy consumption.

    Science.gov (United States)

    Vera, I; Sáez, K; Vidal, G

    2013-01-01

    The performance of 14 Full-Scale Sewage Treatment Plants (STPs) was evaluated. STPs were divided into four aerobic technologies: a) Aerated Lagoon (AL), and three configurations of activated sludge technologies, b) conventional (CAS), c) Extended Aeration (EA), d) Sequencing Batch Reactor (SBR). Comparison between these configurations were made regarding: a) control parameters, organic loading rate (OLR), Mixed Liquor Volatile Suspended Solids (MLVSS) concentrations, Food to Microorganism ratio (F/M), sludge age (theta(c)), Hydraulic Retention Time (HRT) and return sludge ratio (R); b) effluent quality, through 5-day Biological Oxygen Demand (BOD5), Chemical Oxygen Demand (COD), Total Suspended Solids (TSS), Total Kjeldahl Nitrogen (TKN), Total Phosphorus (TP); and c) indicators related to sludge production (on a dry basis) and electrical energy consumption. Also, complementary costs analyses were made. The results show that in terms of effluent quality, for all configurations organic matter (BOD5 and COD) and TKN removal efficiency were up to 90%, while TSS and TP were up to 90% and 50%, respectively. However, CAS, EA, SBR, and AL had stability problems with effluent concentrations. The results of the electrical energy consumption and sludge production analyses show that SBRs reduce these indicators by 40%. Cost analysis showed that CAS, EA, SBR and AL had similar cost structures, with more than 50% of total operating and maintenance cost being related to electrical energy and sludge management. Therefore, SBR could be defined as the configuration with a more stable performance. PMID:24350481

  12. The effects of aging, physical training, and a single bout of exercise on mitochondrial protein expression in human skeletal muscle

    OpenAIRE

    Bori, Zoltan; Zhao, Zhongfu; Koltai, Erika; Fatouros, Ioannis G.; JAMURTAS, ATHANASIOS Z.; Douroudos, Ioannis I.; Terzis, Gerasimos; Chatzinikolaou, Athanasios; Sovatzidis, Apostolos; Draganidis, Dimitrios; Boldogh, Istvan; Radak, Zsolt

    2012-01-01

    Aging results in a significant decline in aerobic capacity and impaired mitochondrial function. We have tested the effects of moderate physical activity on aerobic capacity and a single bout of exercise on the expression profile of mitochondrial biogenesis, and fusion and fission related genes in skeletal muscle of human subjects. Physical activity attenuated the aging-associated decline in VO2 max (p

  13. c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function.

    Directory of Open Access Journals (Sweden)

    Lia R Edmunds

    Full Text Available The c-Myc (Myc oncoprotein and AMP-activated protein kinase (AMPK regulate glycolysis and oxidative phosphorylation (Oxphos although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT and ampk-/- (KO murine embryo fibroblasts (MEFs. KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS-based survey capable of quantifying ~40% of all mitochondrial proteins, showed about 15% of them to be AMPK- and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions.

  14. Impairment of mitochondrial energy metabolism of two marine fish by in vitro mercuric chloride exposure

    International Nuclear Information System (INIS)

    Highlights: • Hg levels usually found in contaminated environments may compromise fish metabolism. • Hg impairs both the oxidative phosphorylation and the electron transport chain. • The decrease of F1Fo-ATPase activity confirmed Hg inhibition of ADP phosphorylation. • The decrease of SDH activity supported Hg inhibition of the electron transport chain. • Mitochondrial respiration is a suitable biomarker of exposure to Hg. - Abstract: The goal of this work was to understand the extent of mercury toxic effects in liver metabolism under an episode of acute contamination. Hence, the effects of in vitro mercuric chloride in liver mitochondria were assessed in two commercial marine fish: Senegalese sole (Solea senegalensis) and gilthead seabream (Sparus aurata). Liver mitochondria were exposed to 0.2 mg L−1 of mercury, the average concentration found in fish inhabiting contaminated areas. Mercuric chloride depressed mitochondrial respiration state 3 and the maximal oxygen consumption in the presence of FCCP indicating inhibitory effects on the oxidative phosphorylation and on the electron transport chain, respectively. The inhibition of F1Fo-ATPase and succinate-dehydrogenase activities also corroborated the ability of mercury to inhibit ADP phosphorylation and the electron transport chain. This study brings new understanding on the mercury levels able to impair fish mitochondrial function, reinforcing the need for further assessing bioenergetics as a proxy for fish health status

  15. Mitochondrial-targeted fluorescent probes for reactive oxygen species

    OpenAIRE

    Dickinson, Bryan C; Srikun, Duangkhae; Chang, Christopher J.

    2009-01-01

    As the primary consumers of oxygen within all aerobic organisms, mitochondria are a major source of cellular reactive oxygen species (ROS) derived from the in vivo chemistry of oxygen metabolism. Mitochondrial ROS have been traditionally implicated in aging and in a variety of pathologies, including cancer, neurodegeneration, and diabetes, but recent studies also link controlled mitochondrial ROS fluxes to cell regulation and signaling events. Progress in the development of mitochondrial-targ...

  16. Ghrelin acts as energy status sensor of male reproduction by modulating Sertoli cells glycolytic metabolism and mitochondrial bioenergetics.

    Science.gov (United States)

    Martins, A D; Sá, R; Monteiro, M P; Barros, A; Sousa, M; Carvalho, R A; Silva, B M; Oliveira, P F; Alves, M G

    2016-10-15

    Ghrelin is a growth hormone-releasing peptide that has been suggested to interfere with spermatogenesis, though the underling mechanisms remain unknown. We studied the effect of ghrelin in human Sertoli cells (hSCs) metabolic phenotype. For that, hSCs were exposed to increasing concentrations of ghrelin (20, 100 and 500 pM) mimicking the levels reported in obese, normal weight, and severely undernourished individuals. The metabolite production/consumption was determined. The protein levels of key glycolysis-related transporters and enzymes were assessed. The lactate dehydrogenase (LDH) activity was measured. Mitochondrial complexes protein levels and mitochondria membrane potential were also measured. We showed that hSCs express the growth hormone secretagogue receptor. At the concentration present in the plasma of normal weight men, ghrelin caused a decrease of glucose consumption and mitochondrial membrane potential in hSCs, though LDH activity and lactate production remained unchanged, illustrating an alteration of glycolytic flux efficiency. Exposure of hSCs to levels of ghrelin found in the plasma of severely undernourished individuals decreased pyruvate consumption and mitochondrial complex III protein expression. All concentrations of ghrelin decreased alanine and acetate production by hSCs. Notably, the effects of ghrelin levels found in severely undernourished individuals were more pronounced in hSCs metabolic phenotype highlighting the importance of a proper eating behavior to maintain male reproductive potential. In conclusion, ghrelin acts as an energy status sensor for hSCs in a dose-dependent manner, showing an inverse association with the production of lactate, thus controlling the nutritional support of spermatogenesis. PMID:27392494

  17. What Is Aerobic Dancing?

    Science.gov (United States)

    ... after exercising, see a physician. Common Aerobics Injuries Plantar fasciitis (arch pain) -- Arch pain is often caused by ... rearfoot instability, with excessive pronation, may result in plantar fasciitis. Shoes with proper support in the arch often ...

  18. Mitochondrial metabolism and diabetes

    OpenAIRE

    Kwak, Soo Heon; Park, Kyong Soo; Lee, Ki‐Up; Lee, Hong Kyu

    2010-01-01

    Abstract The oversupply of calories and sedentary lifestyle has resulted in a rapid increase of diabetes prevalence worldwide. During the past two decades, lines of evidence suggest that mitochondrial dysfunction plays a key role in the pathophysiology of diabetes. Mitochondria are vital to most of the eukaryotic cells as they provide energy in the form of adenosine triphosphate by oxidative phosphorylation. In addition, mitochondrial function is an integral part of glucose‐stimulated insulin...

  19. From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans.

    Science.gov (United States)

    Luz, Anthony L; Godebo, Tewodros R; Bhatt, Dhaval P; Ilkayeva, Olga R; Maurer, Laura L; Hirschey, Matthew D; Meyer, Joel N

    2016-08-01

    Millions of people worldwide are chronically exposed to arsenic through contaminated drinking water. Despite decades of research studying the carcinogenic potential of arsenic, the mechanisms by which arsenic causes cancer and other diseases remain poorly understood. Mitochondria appear to be an important target of arsenic toxicity. The trivalent arsenical, arsenite, can induce mitochondrial reactive oxygen species production, inhibit enzymes involved in energy metabolism, and induce aerobic glycolysis in vitro, suggesting that metabolic dysfunction may be important in arsenic-induced disease. Here, using the model organism Caenorhabditis elegans and a novel metabolic inhibition assay, we report an in vivo induction of aerobic glycolysis following arsenite exposure. Furthermore, arsenite exposure induced severe mitochondrial dysfunction, including altered pyruvate metabolism; reduced steady-state ATP levels, ATP-linked respiration and spare respiratory capacity; and increased proton leak. We also found evidence that induction of autophagy is an important protective response to arsenite exposure. Because these results demonstrate that mitochondria are an important in vivo target of arsenite toxicity, we hypothesized that deficiencies in mitochondrial electron transport chain genes, which cause mitochondrial disease in humans, would sensitize nematodes to arsenite. In agreement with this, nematodes deficient in electron transport chain complexes I, II, and III, but not ATP synthase, were sensitive to arsenite exposure, thus identifying a novel class of gene-environment interactions that warrant further investigation in the human populace.

  20. Methods to determine aerobic endurance.

    Science.gov (United States)

    Bosquet, Laurent; Léger, Luc; Legros, Patrick

    2002-01-01

    Physiological testing of elite athletes requires the correct identification and assessment of sports-specific underlying factors. It is now recognised that performance in long-distance events is determined by maximal oxygen uptake (V(2 max)), energy cost of exercise and the maximal fractional utilisation of V(2 max) in any realised performance or as a corollary a set percentage of V(2 max) that could be endured as long as possible. This later ability is defined as endurance, and more precisely aerobic endurance, since V(2 max) sets the upper limit of aerobic pathway. It should be distinguished from endurance ability or endurance performance, which are synonymous with performance in long-distance events. The present review examines methods available in the literature to assess aerobic endurance. They are numerous and can be classified into two categories, namely direct and indirect methods. Direct methods bring together all indices that allow either a complete or a partial representation of the power-duration relationship, while indirect methods revolve around the determination of the so-called anaerobic threshold (AT). With regard to direct methods, performance in a series of tests provides a more complete and presumably more valid description of the power-duration relationship than performance in a single test, even if both approaches are well correlated with each other. However, the question remains open to determine which systems model should be employed among the several available in the literature, and how to use them in the prescription of training intensities. As for indirect methods, there is quantitative accumulation of data supporting the utilisation of the AT to assess aerobic endurance and to prescribe training intensities. However, it appears that: there is no unique intensity corresponding to the AT, since criteria available in the literature provide inconsistent results; and the non-invasive determination of the AT using ventilatory and heart rate

  1. Integrated model of reaction rate equations and thermal energy balance in aerobic bioreactor for food waste decomposition.

    Science.gov (United States)

    Watanabe, Osamu; Isoda, Satoru

    2011-06-01

    The integrated model is composed of two basic parts: one is a reaction rate model of biodegradation in combination with bioenergetics and the other is a thermal engineering model of energy flow and balance in the bioreactor. Integrating these models provides possibility to estimate microbial activity using time course of physicochemical parameters such as bed temperature, bed weight, and/or C02 concentration during decomposition.

  2. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer.

    Science.gov (United States)

    Hsu, Yi-Chao; Wu, Yu-Ting; Yu, Ting-Hsien; Wei, Yau-Huei

    2016-04-01

    Mesenchymal stem cells (MSCs) are characterized to have the capacity of self-renewal and the potential to differentiate into mesoderm, ectoderm-like and endoderm-like cells. MSCs hold great promise for cell therapies due to their multipotency in vitro and therapeutic advantage of hypo-immunogenicity and lower tumorigenicity. Moreover, it has been shown that MSCs can serve as a vehicle to transfer mitochondria into cells after cell transplantation. Mitochondria produce most of the energy through oxidative phosphorylation in differentiated cells. It has been increasingly clear that the switch of energy supply from glycolysis to aerobic metabolism is essential for successful differentiation of MSCs. Post-translational modifications of proteins have been established to regulate mitochondrial function and metabolic shift during MSCs differentiation. In this article, we review and provide an integrated view on the roles of different protein kinases and sirtuins in the maintenance and differentiation of MSCs. Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of mitochondrial function and adipogenic differentiation of adipose-derived MSCs. We summarize their roles in the regulation of mitochondrial biogenesis and metabolism, oxidative responses and differentiation of MSCs. On the other hand, we discuss recent advances in the study of mitochondrial dynamics and mitochondrial transfer as well as their roles in the differentiation and therapeutic application of MSCs to improve cell function in vitro and in animal models. Accumulating evidence has substantiated that the therapeutic potential of MSCs is conferred not only by cell replacement and paracrine effects but also by transferring mitochondria into injured tissues or cells to modulate the cellular metabolism in situ. Therefore, elucidation of the underlying mechanisms

  3. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer.

    Science.gov (United States)

    Hsu, Yi-Chao; Wu, Yu-Ting; Yu, Ting-Hsien; Wei, Yau-Huei

    2016-04-01

    Mesenchymal stem cells (MSCs) are characterized to have the capacity of self-renewal and the potential to differentiate into mesoderm, ectoderm-like and endoderm-like cells. MSCs hold great promise for cell therapies due to their multipotency in vitro and therapeutic advantage of hypo-immunogenicity and lower tumorigenicity. Moreover, it has been shown that MSCs can serve as a vehicle to transfer mitochondria into cells after cell transplantation. Mitochondria produce most of the energy through oxidative phosphorylation in differentiated cells. It has been increasingly clear that the switch of energy supply from glycolysis to aerobic metabolism is essential for successful differentiation of MSCs. Post-translational modifications of proteins have been established to regulate mitochondrial function and metabolic shift during MSCs differentiation. In this article, we review and provide an integrated view on the roles of different protein kinases and sirtuins in the maintenance and differentiation of MSCs. Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of mitochondrial function and adipogenic differentiation of adipose-derived MSCs. We summarize their roles in the regulation of mitochondrial biogenesis and metabolism, oxidative responses and differentiation of MSCs. On the other hand, we discuss recent advances in the study of mitochondrial dynamics and mitochondrial transfer as well as their roles in the differentiation and therapeutic application of MSCs to improve cell function in vitro and in animal models. Accumulating evidence has substantiated that the therapeutic potential of MSCs is conferred not only by cell replacement and paracrine effects but also by transferring mitochondria into injured tissues or cells to modulate the cellular metabolism in situ. Therefore, elucidation of the underlying mechanisms

  4. Cyanide toxicity in hepatocytes under aerobic and anaerobic conditions.

    Science.gov (United States)

    Aw, T Y; Jones, D P

    1989-09-01

    The effect of cyanide on cell viability and mitochondrial function was studied in hepatocytes exposed to air or argon. Cells were more susceptible to cyanide toxicity under air than under argon. Analysis of the disposition of cyanide showed that the difference in susceptibility to KCN was not due to O2-dependent differences in cyanide metabolism or elimination. Studies of mitochondrial function revealed that cyanide under aerobic conditions resulted in substantial swelling of the mitochondria, which corresponded to a matrix loading of phosphate. In addition, cyanide caused a loss of the mitochondrial protonmotive force. This was in contrast to the results for cells exposed to 30 min of anoxia alone in which there was no loss of mitochondrial delta pH, no detectable change in mitochondrial volume, and little matrix loading of phosphate. These results show that at least some of the protective mechanisms elicited by anoxia (B. S. Andersson, T. Y. Aw, and D. P. Jones. Am. J. Physiol. 252 (Cell Physiol. 21): C349-C355, 1987) are not elicited by cyanide alone. Thus cyanide under aerobic conditions does not provide a completely valid model for simple anoxia. Moreover, the results suggest that the molecular sensor necessary to signal suppression of metabolic and transport functions during neahypoxia is dependent on O2 and is neither stimulated nor antagonized by KCN. PMID:2782387

  5. Mitochondrial Myopathy

    Science.gov (United States)

    ... NINDS supports research focused on effective treatments and cures for mitochondrial myopathies and other mitochondrial diseases. Scientists are investigating the possible benefits of exercise programs and nutritional supplements, primarily natural and synthetic versions of CoQ10. While CoQ10 has ...

  6. Mitochondrial Function and Energy Metabolism in Umbilical Cord Blood- and Bone Marrow-Derived Mesenchymal Stem Cells

    OpenAIRE

    Pietilä, Mika; Palomäki, Sami; Lehtonen, Siri; Ritamo, Ilja; Valmu, Leena; Nystedt, Johanna; Laitinen, Saara; Leskelä, Hannnu-Ville; Sormunen, Raija; Pesälä, Juha; Nordström, Katrina; Vepsäläinen, Ari; Lehenkari, Petri

    2011-01-01

    Human mesenchymal stem cells (hMSCs) are an attractive choice for a variety of cellular therapies. hMSCs can be isolated from many different tissues and possess unique mitochondrial properties that can be used to determine their differentiation potential. Mitochondrial properties may possibly be used as a quality measure of hMSC-based products. Accordingly, the present work focuses on the mitochondrial function of hMSCs from umbilical cord blood (UCBMSC) cells and bone marrow cells from donor...

  7. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

    Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS

  8. Effects of ingesting JavaFit Energy Extreme functional coffee on aerobic and anaerobic fitness markers in recreationally-active coffee consumers.

    Science.gov (United States)

    Roberts, Michael D; Taylor, Lemuel W; Wismann, Jennifer A; Wilborn, Colin D; Kreider, Richard B; Willoughby, Darryn S

    2007-01-01

    The purpose of this study was to examine the effects of ingesting JavaFittrade mark Energy Extreme (JEE) on aerobic and anaerobic performance measures in recreationally-active male and female coffee drinkers. Five male (27.6 +/- 4.2 yrs, 93.2 +/- 11.7 kg, 181.6 +/- 6.9 cm) and five female (29 +/- 4.6 yrs, 61.5 +/- 9.2 kg, 167.6 +/- 6.9 cm) regular coffee drinkers (i.e., 223.9 +/- 62.7 mg.d-1 of caffeine) participated in this study. In a cross-over, randomized design, participants performed a baseline (BASELINE) graded treadmill test (GXT) for peak VO2 assessment and a Wingate test for peak power. Approximately 3-4 d following BASELINE testing, participants returned to the lab for the first trial and ingested 354 ml of either JEE or decaffeinated coffee (DECAF), after which they performed a GXT and Wingate test. Criterion measures during the GXT included an assessment of peakVO2 at maximal exercise, as well as VO2 at 3 minutes and 10 minutes post-exercise. Additionally, time-to-exhaustion (TTE), maximal RPE, mean heart rate (HR), mean systolic pressure (SBP), and mean diastolic blood pressure (DBP) were measured during each condition. Criterion measures for the Wingate included mean HR, SBP, DBP, peak power, and time to peak power (TTP). Participants then returned to the lab approximately one week later to perform the second trial under the same conditions as the first, except consuming the remaining coffee. Data were analyzed using a one way ANOVA (p < 0.05). Our results indicate that JEE significantly increased VO2 at 3 minutes post-exercise when compared to BASELINE (p = 0.04) and DECAF (p = 0.02) values, which may be beneficial in enhancing post-exercise fat metabolism. PMID:18067677

  9. Effects of ingesting JavaFit Energy Extreme functional coffee on aerobic and anaerobic fitness markers in recreationally-active coffee consumers

    Directory of Open Access Journals (Sweden)

    Kreider Richard B

    2007-12-01

    Full Text Available Abstract The purpose of this study was to examine the effects of ingesting JavaFit™ Energy Extreme (JEE on aerobic and anaerobic performance measures in recreationally-active male and female coffee drinkers. Five male (27.6 ± 4.2 yrs, 93.2 ± 11.7 kg, 181.6 ± 6.9 cm and five female (29 ± 4.6 yrs, 61.5 ± 9.2 kg, 167.6 ± 6.9 cm regular coffee drinkers (i.e., 223.9 ± 62.7 mg·d-1 of caffeine participated in this study. In a cross-over, randomized design, participants performed a baseline (BASELINE graded treadmill test (GXT for peak VO2 assessment and a Wingate test for peak power. Approximately 3–4 d following BASELINE testing, participants returned to the lab for the first trial and ingested 354 ml of either JEE or decaffeinated coffee (DECAF, after which they performed a GXT and Wingate test. Criterion measures during the GXT included an assessment of peakVO2 at maximal exercise, as well as VO2 at 3 minutes and 10 minutes post-exercise. Additionally, time-to-exhaustion (TTE, maximal RPE, mean heart rate (HR, mean systolic pressure (SBP, and mean diastolic blood pressure (DBP were measured during each condition. Criterion measures for the Wingate included mean HR, SBP, DBP, peak power, and time to peak power (TTP. Participants then returned to the lab approximately one week later to perform the second trial under the same conditions as the first, except consuming the remaining coffee. Data were analyzed using a one way ANOVA (p 2 at 3 minutes post-exercise when compared to BASELINE (p = 0.04 and DECAF (p = 0.02 values, which may be beneficial in enhancing post-exercise fat metabolism.

  10. Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion.

    Science.gov (United States)

    Shen, Bo; He, Pei-Jie; Shao, Chun-Lin

    2013-01-01

    Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP. PMID:24367681

  11. Norcantharidin induced DU145 cell apoptosis through ROS-mediated mitochondrial dysfunction and energy depletion.

    Directory of Open Access Journals (Sweden)

    Bo Shen

    Full Text Available Norcantharidin (NCTD, a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM, the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN. Moreover, the cells could be killed in a dose-/time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen expression, destruction of mitochondrial membrane potential (MMP, down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5'-monophosphate -activated protein kinase . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.

  12. Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Tetsuhiro, E-mail: atetsu@mail.ecc.u-tokyo.ac.jp; Shimizu, Ayano; Takahashi, Kazutoshi; Hidaka, Makoto; Masaki, Haruhiko, E-mail: amasaki@mail.ecc.u-tokyo.ac.jp

    2014-08-15

    Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ{sup 0} cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.

  13. Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

    International Nuclear Information System (INIS)

    Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ0 cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed

  14. Rats bred for low aerobic capacity become promptly fatigued and have slow metabolic recovery after stimulated, maximal muscle contractions.

    Directory of Open Access Journals (Sweden)

    Sira Torvinen

    Full Text Available AIM: Muscular fatigue is a complex phenomenon affected by muscle fiber type and several metabolic and ionic changes within myocytes. Mitochondria are the main determinants of muscle oxidative capacity which is also one determinant of muscle fatigability. By measuring the concentrations of intracellular stores of high-energy phosphates it is possible to estimate the energy production efficiency and metabolic recovery of the muscle. Low intrinsic aerobic capacity is known to be associated with reduced mitochondrial function. Whether low intrinsic aerobic capacity also results in slower metabolic recovery of skeletal muscle is not known. Here we studied the influence of intrinsic aerobic capacity on in vivo muscle metabolism during maximal, fatiguing electrical stimulation. METHODS: Animal subjects were genetically heterogeneous rats selectively bred to differ for non-trained treadmill running endurance, low capacity runners (LCRs and high capacity runners (HCRs (n = 15-19. We measured the concentrations of major phosphorus compounds and force parameters in a contracting triceps surae muscle complex using (31P-Magnetic resonance spectroscopy ((31P-MRS combined with muscle force measurement from repeated isometric twitches. RESULTS: Our results demonstrated that phosphocreatine re-synthesis after maximal muscle stimulation was significantly slower in LCRs (p<0.05. LCR rats also became promptly fatigued and maintained the intramuscular pH poorly compared to HCRs. Half relaxation time (HRT of the triceps surae was significantly longer in LCRs throughout the stimulation protocol (p≤0.05 and maximal rate of torque development (MRTD was significantly lower in LCRs compared to HCRs from 2 min 30 s onwards (p≤0.05. CONCLUSION: We observed that LCRs are more sensitive to fatigue and have slower metabolic recovery compared to HCRs after maximal muscle contractions. These new findings are associated with reduced running capacity and with previously found

  15. SYNAPTOSOMAL LACTATE DEHYDROGENASE ISOENZYME COMPOSITION IS SHIFTED TOWARD AEROBIC FORMS IN PRIMATE BRAIN EVOLUTION

    Science.gov (United States)

    Duka, Tetyana; Anderson, Sarah M.; Collins, Zachary; Raghanti, Mary Ann; Ely, John J.; Hof, Patrick R.; Wildman, Derek E.; Goodman, Morris; Grossman, Lawrence I.; Sherwood, Chet C.

    2014-01-01

    With the evolution of a relatively large brain size in haplorhine primates (i.e., tarsiers, monkeys, apes and humans), there have been associated changes in the molecular machinery that delivers energy to the neocortex. Here we investigated variation in lactate dehydrogenase (LDH) expression and isoenzyme composition of the neocortex and striatum in primates using quantitative Western blotting and isoenzyme analysis of total homogenates and synaptosomal fractions. Analysis of isoform expression revealed that LDH in the synaptosomal fraction from both forebrain regions shifted towards a predominance of the heart-type, aerobic isoforms, LDHB, among haplorhines as compared to strepsirrhines (i.e., lorises and lemurs), while in total homogenate of neocortex and striatum there was no significant difference in the LDH isoenzyme composition between the primate suborders. The largest increase occurred in synapse-associated LDH-B expression in the neocortex, displaying an especially remarkable elevation in the ratio of LDH-B to LDH-A in humans. The phylogenetic variation in LDH-B to LDH-A ratio was correlated with species typical brain mass, but not encephalization quotient. A significant LDHB increase in the sub-neuronal fraction from haplorhine neocortex and striatum suggests a relatively higher rate of aerobic glycolysis that is linked to synaptosomal mitochondrial metabolism. Our results indicate that there is differential composition of LDH isoenzymes and metabolism in synaptic terminals that evolved in primates to meet increased energy requirements in association with brain enlargement. PMID:24686273

  16. A Mitochondrial Membrane Exopolyphosphatase Is Modulated by, and Plays a Role in, the Energy Metabolism of Hard Tick Rhipicephalus (Boophilus microplus Embryos

    Directory of Open Access Journals (Sweden)

    Carlos Logullo

    2011-06-01

    Full Text Available The physiological roles of polyphosphates (polyP recently found in arthropod mitochondria remain obscure. Here, the relationship between the mitochondrial membrane exopolyphosphatase (PPX and the energy metabolism of hard tick Rhipicephalus microplus embryos are investigated. Mitochondrial respiration was activated by adenosine diphosphate using polyP as the only source of inorganic phosphate (Pi and this activation was much greater using polyP3 than polyP15. After mitochondrial subfractionation, most of the PPX activity was recovered in the membrane fraction and its kinetic analysis revealed that the affinity for polyP3 was 10 times stronger than that for polyP15. Membrane PPX activity was also increased in the presence of the respiratory substrate pyruvic acid and after addition of the protonophore carbonyl cyanide-p-trifluoromethoxyphenylhydrazone. Furthermore, these stimulatory effects disappeared upon addition of the cytochrome oxidase inhibitor potassium cyanide and the activity was completely inhibited by 20 µg/mL heparin. The activity was either increased or decreased by 50% upon addition of dithiothreitol or hydrogen peroxide, respectively, suggesting redox regulation. These results indicate a PPX activity that is regulated during mitochondrial respiration and that plays a role in adenosine-5’-triphosphate synthesis in hard tick embryos.

  17. Adaptation of Mitochondrial Dynamics Is Probably Involved in Aerobic Exercise Prevention of Insulin Resistance Induced by High-fat-diets in Mice%有氧运动改善高脂膳食诱导的胰岛素抵抗:增强骨骼肌线粒体融合与分裂及功能

    Institute of Scientific and Technical Information of China (English)

    赵斐; 靳庆勋; 乔海荣; 张勇

    2012-01-01

    目的:研究高脂膳食诱导胰岛素抵抗(IR)发生中骨骼肌线粒体融合与分裂的改变和长期耐力训练对其影响,为深入探讨IR发生的分子病理学机制以及运动防治IR的机制提供依据.方法:雄性C57BL/6小鼠通过8周高脂膳食诱导IR,再分别将正常和IR小鼠分为安静组和运动组,即正常膳食对照组(NS)、正常膳食运动组(NE)、高脂膳食对照组(HS)、高脂膳食运动组(HE),各运动组进行8周有氧运动训练.检测空腹血糖、胰岛素.提取骨骼肌线粒体测定呼吸功能和ATP合成酶活力.实时荧光定量PCR和Western blot分别测定骨骼肌Mfn2、Opa1、Drp1、Fis1的mRNA和蛋白表达.结果: (1) HS组小鼠空腹血糖、胰岛素和胰岛素抵抗指数均显著高于NS组(P<0.01);骨骼肌线粒体态3呼吸速率、呼吸控制比和ATP酶合成活力均显著低于NS组(P<0.01);Mfn2蛋白显著低于NS组(P<0.01),Drp1和Fis1显著高于NS组(P<0.01). (2) HE组小鼠空腹血糖、胰岛素和胰岛素抵抗指数均显著高于HS组(P<0.01);骨骼肌线粒体态3呼吸速率、RCR和ATP酶合成活力均显著高于HS组(P<0.01);Mfn2、Opa1和Drp1蛋白显著高于HS组(P<0.01,P<0.05,P<0.01).结论:高脂膳食诱导IR的小鼠骨骼肌线粒体趋于分裂,呼吸功能和ATP合成能力下降,可能是高脂膳食诱导IR的机制之一.长期有氧运动训练使正常和IR小鼠骨骼肌线粒体融合和分裂均增强,促进线粒体呼吸功能和ATP合成能力,有利于预防和改善IR.%Objective To investigate the effect of long-term aerobic exercise on skeletal muscle mitochondrial dynamics (fusion and fission) and its function on insulin resistance (IR) induced by high-fat-diet in mice. Methods C57BL/6 mice were fed with high fat diet for 8 weeks to induce IR. Then, normal mice and IR mice divided into 4 groups: normal diet control (NS) , normal diet plus exercise (NE) , high-fat diet control (HS) and high-fat diet plus

  18. MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals

    OpenAIRE

    Wredenberg, Anna; Lagouge, Marie; Bratic, Ana; Metodiev, Metodi D; Spåhr, Henrik; Mourier, Arnaud; Freyer, Christoph; Ruzzenente, Benedetta; Tain, Luke; Grönke, Sebastian; Baggio, Francesca; Kukat, Christian; Kremmer, Elisabeth; Wibom, Rolf; Polosa, Paola Loguercio

    2013-01-01

    Author Summary One of the main functions of the mitochondrial network is to provide the energy currency ATP to drive a large array of cellular metabolic processes. The formation of the mitochondrial respiratory chain, which allows this energy supply, is under the control of two separate genetic systems, the nuclear and the mitochondrial genomes, whose expressions have to be tightly coordinated to ensure efficient mitochondrial function. The regulation of mitochondrial genome expression is sti...

  19. The energy blockers bromopyruvate and lonidamine lead GL15 glioblastoma cells to death by different p53-dependent routes

    OpenAIRE

    Magdalena Davidescu; Lara Macchioni; Gaetano Scaramozzino; Maria Cristina Marchetti; Graziella Migliorati; Rita Vitale; Angela Corcelli; Rita Roberti; Emilia Castigli; Lanfranco Corazzi

    2015-01-01

    The energy metabolism of tumor cells relies on aerobic glycolysis rather than mitochondrial oxidation. This difference between normal and cancer cells provides a biochemical basis for new therapeutic strategies aimed to block the energy power plants of cells. The effects produced by the energy blockers bromopyruvate (3BP) and lonidamine (LND) and the underlying biochemical mechanisms were investigated in GL15 glioblastoma cells. 3BP exerts early effects compared to LND, even though both drugs...

  20. Regulation of the cell cycle via mitochondrial gene expression and energy metabolism in HeLa cells

    Institute of Scientific and Technical Information of China (English)

    Wei Xiong; Yang Jiao; Weiwei Huang; Mingxing Ma; Min Yu; Qinghua Cui; Deyong Tan

    2012-01-01

    Human cervical cancer HeLa cells have functional mitochondria.Recent studies have suggested that mitochondrial metabolism plays an essential role in tumor cell proliferation.Nevertheless,how cells coordinate mitochondrial dynamics and cell cycle progression remains to be clarified.To investigate the relationship between mitochondrial function and cell cycle regulation,the mitochondrial gene expression profile and cellular ATP levels were determined by cell cycle progress analysis in the present study.HeLa cells were synchronized in the G0/G1 phase by serum starvation,and re-entered cell cycle by restoring serum culture,time course experiment was performed to analyze the expression of mitochondrial transcription regulators and mitochondrial genes,mitochondrial membrane potential (MMP),cellular ATP levels,and cell cycle progression.The results showed that when arrested G0/G1 cells were stimulated in serum-containing medium,the amount of DNA and the expression levels of both mRNA and proteins in mitochondria started to increase at 2 h time point,whereas the MMP and ATP level elevated at 4 h.Furthermore,the cyclin D1 expression began to increase at 4 h after serum triggered cell cycle.ATP synthesis inhibitor-oligomycintreatment suppressed the cyclin D1 and cyclin B1 expression levels and blocked cell cycle progression.Taken together,our results suggested that increased mitochondrial gene expression levels,oxidative phosphorylation activation,and cellular ATP content increase are important events for triggering cell cycle.Finally,we demonstrated that mitochondrial gene expression levels and cellular ATP content are tightly regulated and might play a central role in regulating cell proliferation.

  1. Control of lipid oxidation during exercise: role of energy state and mitochondrial factors

    DEFF Research Database (Denmark)

    Sahlin, K; Harris, R C

    2008-01-01

    Despite considerable progress during recent years our understanding of how lipid oxidation (LOx) is controlled during exercise remains incomplete. This review focuses on the role of mitochondria and energy state in the control of LOx. LOx increases in parallel with increased energy demand up...... and CHO oxidation and relative fuel utilization is mainly controlled by substrate availability and the capacity of the metabolic pathways. In the high-intensity domain (>60%VO(2max)) there is a pronounced decrease in energy state, which will stimulate glycolysis in excess of the substrate requirements...... of the oxidative processes. This will lead to acidosis, reduced levels of free Coenzyme A (CoASH) and reduced levels of free carnitine. Acidosis and reduced carnitine may limit the carnitine-mediated transfer of long-chain fatty acids (LCFA) into mitochondria and may thus explain the observed reduction in LOx...

  2. BAX supports the mitochondrial network, promoting bioenergetics in nonapoptotic cells

    Science.gov (United States)

    Boohaker, Rebecca J.; Zhang, Ge; Carlson, Adina Loosley; Nemec, Kathleen N.

    2011-01-01

    The dual functionality of the tumor suppressor BAX is implied by the nonapoptotic functions of other members of the BCL-2 family. To explore this, mitochondrial metabolism was examined in BAX-deficient HCT-116 cells as well as primary hepatocytes from BAX-deficient mice. Although mitochondrial density and mitochondrial DNA content were the same in BAX-containing and BAX-deficient cells, MitoTracker staining patterns differed, suggesting the existence of BAX-dependent functional differences in mitochondrial physiology. Oxygen consumption and cellular ATP levels were reduced in BAX-deficient cells, while glycolysis was increased. These results suggested that cells lacking BAX have a deficiency in the ability to generate ATP through cellular respiration. This conclusion was supported by detection of reduced citrate synthase activity in BAX-deficient cells. In nonapoptotic cells, a portion of BAX associated with mitochondria and a sequestered, protease-resistant form was detected. Inhibition of BAX with small interfering RNAs reduced intracellular ATP content in BAX-containing cells. Expression of either full-length or COOH-terminal-truncated BAX in BAX-deficient cells rescued ATP synthesis and oxygen consumption and reduced glycolytic activity, suggesting that this metabolic function of BAX was not dependent upon its COOH-terminal helix. Expression of BCL-2 in BAX-containing cells resulted in a subsequent loss of ATP measured, implying that, even under nonapoptotic conditions, an antagonistic interaction exists between the two proteins. These findings infer that a basal amount of BAX is necessary to maintain energy production via aerobic respiration. PMID:21289292

  3. Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening.

    Science.gov (United States)

    Orr, Adam L; Ashok, Deepthi; Sarantos, Melissa R; Shi, Tong; Hughes, Robert E; Brand, Martin D

    2013-12-01

    Mitochondrial production of reactive oxygen species is often considered an unavoidable consequence of aerobic metabolism and currently cannot be manipulated without perturbing oxidative phosphorylation. Antioxidants are widely used to suppress effects of reactive oxygen species after formation, but they can never fully prevent immediate effects at the sites of production. To identify site-selective inhibitors of mitochondrial superoxide/H2O2 production that do not interfere with mitochondrial energy metabolism, we developed a robust small-molecule screen and secondary profiling strategy. We describe the discovery and characterization of a compound (N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide; CN-POBS) that selectively inhibits superoxide/H2O2 production from the ubiquinone-binding site of complex I (site I(Q)) with no effects on superoxide/H2O2 production from other sites or on oxidative phosphorylation. Structure/activity studies identified a core structure that is important for potency and selectivity for site I(Q). By employing CN-POBS in mitochondria respiring on NADH-generating substrates, we show that site I(Q) does not produce significant amounts of superoxide/H2O2 during forward electron transport on glutamate plus malate. Our screening platform promises to facilitate further discovery of direct modulators of mitochondrially derived oxidative damage and advance our ability to understand and manipulate mitochondrial reactive oxygen species production under both normal and pathological conditions. PMID:23994103

  4. The mitochondrial pyruvate carrier in health and disease: To carry or not to carry?

    Science.gov (United States)

    Bender, Tom; Martinou, Jean-Claude

    2016-10-01

    Mitochondria play a key role in energy metabolism, hosting the machinery for oxidative phosphorylation, the most efficient cellular pathway for generating ATP. A major checkpoint in this process is the transport of pyruvate produced by cytosolic glycolysis into the mitochondrial matrix, which is accomplished by the recently identified mitochondrial pyruvate carrier (MPC). As the gatekeeper for pyruvate entry into mitochondria, the MPC is thought to be of fundamental importance in establishing the metabolic programming of a cell. This is especially relevant in the context of the aerobic glycolysis, also known as the Warburg effect, which is a hallmark in many types of cancer, and MPC loss of function promotes cancer growth. Moreover, mitochondrial pyruvate uptake is needed for efficient hepatic gluconeogenesis and the regulation of blood glucose levels. In this review we discuss recent advances in our knowledge of the MPC, and we argue that it may offer a promising target in diseases like cancer and type 2 diabetes. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.

  5. Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Verónica Loera-Castañeda

    2014-01-01

    Full Text Available Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS. Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12% harbored the A8027G polymorphism and three of them were early onset (EO AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn’t been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD.

  6. Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

    Science.gov (United States)

    Loera-Castañeda, Verónica; Sandoval-Ramírez, Lucila; Pacheco Moisés, Fermín Paul; Macías-Islas, Miguel Ángel; Alatorre Jiménez, Moisés Alejandro; González-Renovato, Erika Daniela; Cortés-Enríquez, Fernando; Célis de la Rosa, Alfredo; Velázquez-Brizuela, Irma E.

    2014-01-01

    Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II) in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12%) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn't been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD. PMID:24701363

  7. Mitochondrial DNA in the regulation of innate immune responses.

    Science.gov (United States)

    Fang, Chunju; Wei, Xiawei; Wei, Yuquan

    2016-01-01

    Mitochondrion is known as the energy factory of the cell, which is also a unique mammalian organelle and considered to be evolved from aerobic prokaryotes more than a billion years ago. Mitochondrial DNA, similar to that of its bacterial ancestor’s, consists of a circular loop and contains significant number of unmethylated DNA as CpG islands. The innate immune system plays an important role in the mammalian immune response. Recent research has demonstrated that mitochondrial DNA (mtDNA) activates several innate immune pathways involving TLR9, NLRP3 and STING signaling, which contributes to the signaling platforms and results in effector responses. In addition to facilitating antibacterial immunity and regulating antiviral signaling, mounting evidence suggests that mtDNA contributes to inflammatory diseases following cellular damage and stress. Therefore, in addition to its well-appreciated roles in cellular metabolism and energy production,mtDNA appears to function as a key member in the innate immune system. Here, we highlight the emerging roles of mtDNA in innate immunity. PMID:26498951

  8. Mitochondrial dysfunction in heart failure.

    Science.gov (United States)

    Rosca, Mariana G; Hoppel, Charles L

    2013-09-01

    Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is considered to be a key contributor to the development of both cardiac and skeletal myopathy. In HF, several components of cardiac and skeletal muscle bioenergetics are altered, such as oxygen availability, substrate oxidation, mitochondrial ATP production, and ATP transfer to the contractile apparatus via the creatine kinase shuttle. This review focuses on alterations in mitochondrial biogenesis and respirasome organization, substrate oxidation coupled with ATP synthesis in the context of their contribution to the chronic energy deficit, and mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that HF is associated with decreased mitochondrial biogenesis and function in both heart and skeletal muscle, supporting the concept of a systemic mitochondrial cytopathy. The sites of mitochondrial defects are located within the electron transport and phosphorylation apparatus and differ with the etiology and progression of HF in the two mitochondrial populations (subsarcolemmal and interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic stimulation, the renin-angiotensin system, and cytokines are evaluated as factors responsible for the systemic energy deficit. We propose a cyclic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction.

  9. Annular purpura and step aerobics.

    Science.gov (United States)

    Allan, S J; Humphreys, F; Buxton, P K

    1994-09-01

    Step aerobic classes are at present one of the most popular forms of exercise undertaken by young adults. To date no dermatological abnormalities have been described in people regularly performing step aerobics. We describe a case in which a healthy young woman developed an extensive pigmented purpuric eruption 4 weeks after commencing regular step aerobic classes. The eruption resolved completely 8 weeks after regular exercise was ceased. PMID:7955503

  10. Mitochondrial Ion Channels

    Science.gov (United States)

    O’Rourke, Brian

    2009-01-01

    In work spanning more than a century, mitochondria have been recognized for their multifunctional roles in metabolism, energy transduction, ion transport, inheritance, signaling, and cell death. Foremost among these tasks is the continuous production of ATP through oxidative phosphorylation, which requires a large electrochemical driving force for protons across the mitochondrial inner membrane. This process requires a membrane with relatively low permeability to ions to minimize energy dissipation. However, a wealth of evidence now indicates that both selective and nonselective ion channels are present in the mitochondrial inner membrane, along with several known channels on the outer membrane. Some of these channels are active under physiological conditions, and others may be activated under pathophysiological conditions to act as the major determinants of cell life and death. This review summarizes research on mitochondrial ion channels and efforts to identify their molecular correlates. Except in a few cases, our understanding of the structure of mitochondrial ion channels is limited, indicating the need for focused discovery in this area. PMID:17059356

  11. Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Hey-Mogensen, Martin; Højlund, K; Vind, B F;

    2010-01-01

    Studies have suggested a link between insulin resistance and mitochondrial dysfunction in skeletal muscles. Our primary aim was to investigate the effect of aerobic training on mitochondrial respiration and mitochondrial reactive oxygen species (ROS) release in skeletal muscle of obese participants...... with and without type 2 diabetes....

  12. Mitochondrial energy metabolism changes during aging-mouse cranial nerve cells treated with various doses and forms of Fructus schizandrae

    Institute of Scientific and Technical Information of China (English)

    Hongyan Guo; Jinhe Li

    2008-01-01

    BACKGROUND: During the cellular aging process, the number of mitochondria, generation of adenosine triphosphate (ATP), activity of respiratory chain enzyme complex 1 and 4, and oxidation decrease. OBJECTIVE: To observe the effects of aqueous and spirituous extract, as well as polysaccharides from Fructus schizandrae (Magnolia Vine) on energy metabolism and mitochondrial anti-oxidation in cranial nerve cells of a D-gal-induccd aging mouse model.DESIGN, TIME AND SETTING: A randomized, controlled, animal study. The experiment was conducted at the Department of Biochemistry, Qiqihar Medical College between March and July 2006.MATERIALS: Fifty healthy, Kunming mice of both sexes, aged 2 3 months old and weighing 18-22 g, were used for the present study. Fructus schizandrae was purchased from the Medical College of Jiamusi University. Aqueous extracts, spirituous extracts, and polysaccharides from Fructus schizandrae were prepared. D-galactose (D-gal) is a product of the Second Reagent Factory, Shanghai City, China. Mn-superoxide dismutase (Mn-SOD) kit, malonaldehyde (MDA) kit, protein quantification kit, and inorganic phosphorus testing kit were purchased from Jian Cheng Bioeng. Co., China.METHODS: Fifty mice were randomly divided into five groups, with 10 mice in each group: young control, aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides. Over a course of 30 days, mice in aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides groups were injected subcutaneously with D-gal (100 mg/kg) into the nape of the neck daily, and administered intragastrically with an equal volume of sterile, warm water (aging model), aqueous Fructus schizandrae extract (2 g/kg), spirituous Fructus schizandrae extract (2 g/kg), or Fructus schizandrae polysaccharides (0.2 g/kg), respectively. Mice in the young control group were injected into

  13. Mitochondrial calcium uptake.

    Science.gov (United States)

    Williams, George S B; Boyman, Liron; Chikando, Aristide C; Khairallah, Ramzi J; Lederer, W J

    2013-06-25

    Calcium (Ca(2+)) uptake into the mitochondrial matrix is critically important to cellular function. As a regulator of matrix Ca(2+) levels, this flux influences energy production and can initiate cell death. If large, this flux could potentially alter intracellular Ca(2+) ([Ca(2+)]i) signals. Despite years of study, fundamental disagreements on the extent and speed of mitochondrial Ca(2+) uptake still exist. Here, we review and quantitatively analyze mitochondrial Ca(2+) uptake fluxes from different tissues and interpret the results with respect to the recently proposed mitochondrial Ca(2+) uniporter (MCU) candidate. This quantitative analysis yields four clear results: (i) under physiological conditions, Ca(2+) influx into the mitochondria via the MCU is small relative to other cytosolic Ca(2+) extrusion pathways; (ii) single MCU conductance is ∼6-7 pS (105 mM [Ca(2+)]), and MCU flux appears to be modulated by [Ca(2+)]i, suggesting Ca(2+) regulation of MCU open probability (P(O)); (iii) in the heart, two features are clear: the number of MCU channels per mitochondrion can be calculated, and MCU probability is low under normal conditions; and (iv) in skeletal muscle and liver cells, uptake per mitochondrion varies in magnitude but total uptake per cell still appears to be modest. Based on our analysis of available quantitative data, we conclude that although Ca(2+) critically regulates mitochondrial function, the mitochondria do not act as a significant dynamic buffer of cytosolic Ca(2+) under physiological conditions. Nevertheless, with prolonged (superphysiological) elevations of [Ca(2+)]i, mitochondrial Ca(2+) uptake can increase 10- to 1,000-fold and begin to shape [Ca(2+)]i dynamics.

  14. Aerobic landfill bioreactor

    Science.gov (United States)

    Hudgins, Mark P; Bessette, Bernard J; March, John; McComb, Scott T.

    2000-01-01

    The present invention includes a method of decomposing municipal solid waste (MSW) within a landfill by converting the landfill to aerobic degradation in the following manner: (1) injecting air via the landfill leachate collection system (2) injecting air via vertical air injection wells installed within the waste mass; (3) applying leachate to the waste mass using a pressurized drip irrigation system; (4) allowing landfill gases to vent; and (5) adjusting air injection and recirculated leachate to achieve a 40% to 60% moisture level and a temperature between 120.degree. F. and 140.degree. F. in steady state.

  15. DAMAGE TO MITOCHONDRIAL ELECTRON TRANSPORT AND ENERGY COUPLING BY VISIBLE LIGHT

    Energy Technology Data Exchange (ETDEWEB)

    Aggarwal, B.B.; Quintanilha, A.T.; Cammack, R.; Packer, L.

    1977-09-01

    Plutonium is one of the principal materials of both commercial and military nuclear power. It is produced primarily in fission reactors that contain uranium fuel, and its importance arises from the fact that a large portion of the plutonium produced is fissile: like uranium 235, the mass 239 and 241 isotopes of plutonium can be caused to fission by neutrons, including those with low energy. Because such fission events also release neutrons, substantial amounts of energy can be extracted from plutonium in a controlled or an explosive nuclear chain reaction. Now that commercial nuclear reactors provide a noticeable fraction of United States (and world) electrical energy, these reactors account for most plutonium production. For the most part, this material now remains in the irradiated fuel after removal from reactors, but should this fuel be reprocessed, the plutonium could be recycled to provide part and even most of the fissile content of fresh fuel. For the current generation of water-cooled reactors, the amount of plutonium to be recycled is substantial. In fast breeder reactors, designed to produce more fissile material than they destroy, considerably larger quantities of plutonium would be recycled. In other types of advanced reactors, particularly those which depend heavily on thorium as the material from which fissile material (primarily uranium 233) is produced, the amount of plutonium to be handled would be considerably reduced. Because plutonium is a highly toxic substance, great care is taken to contain it at the sites and facilities where it is stored or handled. In addition, it is necessary that devices be available to monitor any releases from these facilities into environmental media and to measure concentrations of plutonium in these media. The radiation protection standards are so strict for plutonium that only small releases and low concentrations can be tolerated. Such considerations, discussed in the next section, require that monitoring

  16. Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun Hyoung Park

    2016-03-01

    Full Text Available Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple-negative breast cancer (TNBC. Analysis of cybrids and established breast cancer (BC cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β oxidation (FAO and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1A (CPT1 and 2 (CPT2, the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.

  17. Aerobic and Anaerobic Starvation Metabolism in Methanotrophic Bacteria

    OpenAIRE

    Roslev, P.; King, G. M.

    1995-01-01

    The capacity for anaerobic metabolism of endogenous and selected exogenous substrates in carbon- and energy-starved methanotrophic bacteria was examined. The methanotrophic isolate strain WP 12 survived extended starvation under anoxic conditions while metabolizing 10-fold less endogenous substrate than did parallel cultures starved under oxic conditions. During aerobic starvation, the cell biomass decreased by 25% and protein and lipids were the preferred endogenous substrates. Aerobic prote...

  18. The mitochondrial calcium uniporter (MCU): molecular identity and physiological roles.

    Science.gov (United States)

    Patron, Maria; Raffaello, Anna; Granatiero, Veronica; Tosatto, Anna; Merli, Giulia; De Stefani, Diego; Wright, Lauren; Pallafacchina, Giorgia; Terrin, Anna; Mammucari, Cristina; Rizzuto, Rosario

    2013-04-12

    The direct measurement of mitochondrial [Ca(2+)] with highly specific probes demonstrated that major swings in organellar [Ca(2+)] parallel the changes occurring in the cytosol and regulate processes as diverse as aerobic metabolism and cell death by necrosis and apoptosis. Despite great biological relevance, insight was limited by the complete lack of molecular understanding. The situation has changed, and new perspectives have emerged following the very recent identification of the mitochondrial Ca(2+) uniporter, the channel allowing rapid Ca(2+) accumulation across the inner mitochondrial membrane.

  19. [Mitochondrial diseases; thinking beyond organ specialism necessary

    NARCIS (Netherlands)

    Smits, B.W.; Smeitink, J.A.M.; Engelen, B.G.M. van

    2008-01-01

    Mitochondrial disorders are caused by a defect in intracellular energy production. In general, these are multi-system disorders, predominantly affecting organs with high energy requirements. Due to the fact that mitochondrial disorders are not as rare as is generally assumed, and due to the diversit

  20. Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane

    Science.gov (United States)

    2014-01-01

    Background Cancer cells, and a variety of normal cells, exhibit aerobic glycolysis, high rates of glucose fermentation in the presence of normal oxygen concentrations, also known as the Warburg effect. This metabolism is considered abnormal because it violates the standard model of cellular energy production that assumes glucose metabolism is predominantly governed by oxygen concentrations and, therefore, fermentative glycolysis is an emergency back-up for periods of hypoxia. Though several hypotheses have been proposed for the origin of aerobic glycolysis, its biological basis in cancer and normal cells is still not well understood. Results We examined changes in glucose metabolism following perturbations in membrane activity in different normal and tumor cell lines and found that inhibition or activation of pumps on the cell membrane led to reduction or increase in glycolysis, respectively, while oxidative phosphorylation remained unchanged. Computational simulations demonstrated that these findings are consistent with a new model of normal physiological cellular metabolism in which efficient mitochondrial oxidative phosphorylation supplies chronic energy demand primarily for macromolecule synthesis and glycolysis is necessary to supply rapid energy demands primarily to support membrane pumps. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. The predictions were confirmed experimentally. Conclusions Our results show that glycolytic metabolism serves a critical physiological function under normoxic conditions by responding to rapid energetic demand, mainly from membrane transport activities, even in the presence of oxygen. This supports a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Cells use efficient but

  1. Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Michelle Barbi de Moura

    Full Text Available SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. When grown under standard cell culture conditions (25 mM glucose all three sirtuins induced increases in mitochondrial respiration, glycolysis, and glucose oxidation, but with no change in growth rate or in steady-state ATP concentration. Increased proton leak, as evidenced by oxygen consumption in the presence of oligomycin, appeared to explain much of the increase in basal oxygen utilization. Growth in 5 mM glucose normalized the elevations in basal oxygen consumption, proton leak, and glycolysis in all sirtuin over-expressing cells. While the above effects were common to all three mitochondrial sirtuins, some differences between the SIRT3, SIRT4, and SIRT5 expressing cells were noted. Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak.

  2. Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation.

    Directory of Open Access Journals (Sweden)

    Bram J van Raam

    Full Text Available BACKGROUND: Neutrophils depend mainly on glycolysis for their energy provision. Their mitochondria maintain a membrane potential (Deltapsi(m, which is usually generated by the respiratory chain complexes. We investigated the source of Deltapsi(m in neutrophils, as compared to peripheral blood mononuclear leukocytes and HL-60 cells, and whether neutrophils can still utilise this Deltapsi(m for the generation of ATP. METHODS AND PRINCIPAL FINDINGS: Individual activity of the oxidative phosphorylation complexes was significantly reduced in neutrophils, except for complex II and V, but Deltapsi(m was still decreased by inhibition of complex III, confirming the role of the respiratory chain in maintaining Deltapsi(m. Complex V did not maintain Deltapsi(m by consumption of ATP, as has previously been suggested for eosinophils. We show that complex III in neutrophil mitochondria can receive electrons from glycolysis via the glycerol-3-phosphate shuttle. Furthermore, respiratory supercomplexes, which contribute to efficient coupling of the respiratory chain to ATP synthesis, were lacking in neutrophil mitochondria. When HL-60 cells were differentiated to neutrophil-like cells, they lost mitochondrial supercomplex organisation while gaining increased aerobic glycolysis, just like neutrophils. CONCLUSIONS: We show that neutrophils can maintain Deltapsi(m via the glycerol-3-phosphate shuttle, whereby their mitochondria play an important role in the regulation of aerobic glycolysis, rather than producing energy themselves. This peculiar mitochondrial phenotype is acquired during differentiation from myeloid precursors.

  3. What Is Mitochondrial DNA?

    Science.gov (United States)

    ... DNA What is mitochondrial DNA? What is mitochondrial DNA? Although most DNA is packaged in chromosomes within ... proteins. For more information about mitochondria and mitochondrial DNA: Molecular Expressions, a web site from the Florida ...

  4. Mitochondrial dysfunction and organophosphorus compounds

    Energy Technology Data Exchange (ETDEWEB)

    Karami-Mohajeri, Somayyeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  5. Mitochondrial dysfunction and organophosphorus compounds

    International Nuclear Information System (INIS)

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP

  6. Ginsenoside Rg3 improves cardiac mitochondrial population quality: Mimetic exercise training

    International Nuclear Information System (INIS)

    Highlights: •Rg3 is an ergogenic aid. •Rg3 improves mitochondrial antioxidant capacity. •Rg3 regulates mitochondria dynamic remodeling. •Rg3 alone matches some the benefits of aerobic exercise. -- Abstract: Emerging evidence indicates exercise training could mediate mitochondrial quality control through the improvement of mitochondrial dynamics. Ginsenoside Rg3 (Rg3), one of the active ingredients in Panax ginseng, is well known in herbal medicine as a tonic and restorative agent. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. In the present study, we compared the effects of Rg3 administration with aerobic exercise on mitochondrial adaptation in cardiac muscle tissue of Sprague–Dawley (SD) rats. Three groups of SD rats were studied: (1) sedentary control, (2) Rg3-treated and (3) aerobic exercise trained. Both aerobic exercise training and Rg3 supplementation enhanced peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) protein levels in cardiac muscle. The activation of PGC-1α led to increased mRNA levels of mitochondrial transcription factor A (Tfam) and nuclear related factor 1(Nrf1), these changes were accompanied by increases in mitochondrial DNA copy number and complex protein levels, while activation of Nrf2 increased levels of phase II detoxifying enzymes, including nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1(NQO1), superoxide dismutase (MnSOD) and catalase. Aerobic exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of beclin1 and autophagy-related protein 7 (ATG7), these effects of aerobic exercise are comparable to that of Rg3. These results demonstrate that Rg3 mimics improved cardiac adaptations to exercise by regulating mitochondria dynamic remodeling and enhancing the quantity and quality of mitochondria

  7. Ginsenoside Rg3 improves cardiac mitochondrial population quality: Mimetic exercise training

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Mengwei [Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200031 (China); Huang, Chenglin [Shanghai Key Laboratory of Vascular Biology, Department of Hypertension and Pharmacology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Wang, Cheng; Zheng, Jianheng; Zhang, Peng; Xu, Yangshu [Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200031 (China); Chen, Hong, E-mail: hchen100@hotmail.com [Shanghai Key Laboratory of Vascular Biology, Department of Hypertension and Pharmacology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Shen, Weili, E-mail: weili_shen@hotmail.com [Shanghai Key Laboratory of Vascular Biology, Department of Hypertension and Pharmacology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China)

    2013-11-08

    Highlights: •Rg3 is an ergogenic aid. •Rg3 improves mitochondrial antioxidant capacity. •Rg3 regulates mitochondria dynamic remodeling. •Rg3 alone matches some the benefits of aerobic exercise. -- Abstract: Emerging evidence indicates exercise training could mediate mitochondrial quality control through the improvement of mitochondrial dynamics. Ginsenoside Rg3 (Rg3), one of the active ingredients in Panax ginseng, is well known in herbal medicine as a tonic and restorative agent. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. In the present study, we compared the effects of Rg3 administration with aerobic exercise on mitochondrial adaptation in cardiac muscle tissue of Sprague–Dawley (SD) rats. Three groups of SD rats were studied: (1) sedentary control, (2) Rg3-treated and (3) aerobic exercise trained. Both aerobic exercise training and Rg3 supplementation enhanced peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) protein levels in cardiac muscle. The activation of PGC-1α led to increased mRNA levels of mitochondrial transcription factor A (Tfam) and nuclear related factor 1(Nrf1), these changes were accompanied by increases in mitochondrial DNA copy number and complex protein levels, while activation of Nrf2 increased levels of phase II detoxifying enzymes, including nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1(NQO1), superoxide dismutase (MnSOD) and catalase. Aerobic exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of beclin1 and autophagy-related protein 7 (ATG7), these effects of aerobic exercise are comparable to that of Rg3. These results demonstrate that Rg3 mimics improved cardiac adaptations to exercise by regulating mitochondria dynamic remodeling and enhancing the quantity and quality of mitochondria.

  8. The Impaction of Body Energy to the Aerobics Competitor′s Competitive Ability and Compensation%体能对男单竞技健美操运动员竞技能力的功能补偿研究

    Institute of Scientific and Technical Information of China (English)

    李倩

    2014-01-01

    Using the method of literature review,video analysis and statistic analysis,it studied the elements of in individual men competitor of the eighth World Championship,and the execution of elements in each game. The result shows that our competitors of sports aerobics have serious problems on body energy.We should give some training methods of compensation for the undeveloped components.Through these training meth-ods,we expect it can be helpful for the body energy training,and it can offer the player to get the opinion to Aerobics Olymnastics World Cup.%运用文献资料法、录像分析法、数理统计法对第10届竞技健美操世锦赛男单个人难度动作完成情况进行了统计分析,研究发现:我国男单竞技健美操运动员存在一定的体能弱势问题,体能弱势影响了运动员竞技能力的发挥。因此,对体能这一弱势因素提出了一些补偿性训练措施,可以为我国的男单运动员的体能训练提供一定的参考依据,以使其总体竞技能力得到提高。

  9. Brain Plasticity and Aerobic Fitness

    OpenAIRE

    Thomas, Adam G.; Johansen-Berg, Heidi; Bandettini, Peter

    2014-01-01

    Regular aerobic exercise has a wide range of positive effects on health and cognition. Exercise has been demonstrated to provide a particularly powerful and replicable method of triggering a wide range of structural changes within both human and animal brains. However, the details and mechanisms of these changes remain poorly understood. This thesis undertakes a comprehensive examination of the relationship between brain plasticity and aerobic exercise. A large, longitudinal experiment ...

  10. Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.

    Science.gov (United States)

    Deng, Wu; Leu, Hsin-Bang; Chen, Yumay; Chen, Yu-Han; Epperson, Christine M; Juang, Charity; Wang, Ping H

    2014-05-01

    Our previous studies showed that insulin stimulated AKT1 translocation into mitochondria and modulated oxidative phosphorylation complex V in cardiac muscle. This raised the possibility that mitochondrial AKT1 may regulate glycolytic oxidative phosphorylation and mitochondrial function in cardiac muscle cells. The aims of this project were to study the effects of mitochondrial AKT1 signaling on cell survival in stressed cardiomyocytes, to define the effect of mitochondrial AKT1 signaling on glycolytic bioenergetics, and to identify mitochondrial targets of AKT1 signaling in cardiomyocytes. Mitochondrial AKT1 signaling played a protective role against apoptosis and necrosis during ischemia-reperfusion stress, suppressed mitochondrial calcium overload, and alleviated mitochondrial membrane depolarization. Activation of AKT1 signaling in mitochondria increased glucose uptake, enhanced respiration efficiency, reduced superoxide generation, and increased ATP production in the cardiomyocytes. Inhibition of mitochondrial AKT attenuated insulin response, indicating that insulin regulation of ATP production required mitochondrial AKT1 signaling. A proteomic approach was used to reveal 15 novel targets of AKT1 signaling in mitochondria, including pyruvate dehydrogenase complex (PDC). We have confirmed and characterized the association of AKT1 and PDC subunits and verified a stimulatory effect of mitochondrial AKT1 on the enzymatic activity of PDC. These findings suggested that AKT1 formed protein complexes with multiple mitochondrial proteins and improved mitochondrial function in stressed cardiomyocytes. The novel AKT1 signaling targets in mitochondria may become a resource for future metabolism research.

  11. Mitochondrial DNA variants mediate energy production and expression levels for CFH, C3 and EFEMP1 genes: implications for age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    M Cristina Kenney

    Full Text Available BACKGROUND: Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD. Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt DNA haplogroups (as defined by combinations of mtDNA polymorphisms that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD versus J haplogroup (high risk for AMD. METHODOLOGY/PRINCIPAL FINDINGS: Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19 that was devoid of mitochondrial DNA (Rho0. In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD.

  12. Autism Spectrum Disorder and Mitochondrial Disease

    Science.gov (United States)

    ... that the cells need to work. In mitochondrial diseases, the mitochondria cannot efficiently turn sugar and oxygen into energy, so the cells do not work correctly. There are many types of mitochondrial disease, and they can affect different parts of the ...

  13. Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using yeast models of OXPHOS deficiencies.

    Science.gov (United States)

    Fontanesi, Flavia; Diaz, Francisca; Barrientos, Antoni

    2009-10-01

    The oxidative phosphorylation (OXPHOS) system consists of five multimeric complexes embedded in the mitochondrial inner membrane. They work in concert to drive the aerobic synthesis of ATP. Mitochondrial and nuclear DNA mutations affecting the accumulation and function of these enzymes are the most common cause of mitochondrial diseases and have also been associated with neurodegeneration and aging. Several approaches for the assessment of the OXPHOS system enzymes have been developed. Based on the methods described elsewhere, this unit describes the creation and study of yeast models of mitochondrial OXPHOS deficiencies.

  14. Impaired mitochondrial energy metabolism in Alzheimer's disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape.

    Science.gov (United States)

    Salminen, Antero; Haapasalo, Annakaisa; Kauppinen, Anu; Kaarniranta, Kai; Soininen, Hilkka; Hiltunen, Mikko

    2015-08-01

    The amyloid cascade hypothesis for the pathogenesis of Alzheimer's disease (AD) was proposed over twenty years ago. However, the mechanisms of neurodegeneration and synaptic loss have remained elusive delaying the effective drug discovery. Recent studies have revealed that amyloid-β peptides as well as phosphorylated and fragmented tau proteins accumulate within mitochondria. This process triggers mitochondrial fission (fragmentation) and disturbs Krebs cycle function e.g. by inhibiting the activity of 2-oxoglutarate dehydrogenase. Oxidative stress, hypoxia and calcium imbalance also disrupt the function of Krebs cycle in AD brains. Recent studies on epigenetic regulation have revealed that Krebs cycle intermediates control DNA and histone methylation as well as histone acetylation and thus they have fundamental roles in gene expression. DNA demethylases (TET1-3) and histone lysine demethylases (KDM2-7) are included in the family of 2-oxoglutarate-dependent oxygenases (2-OGDO). Interestingly, 2-oxoglutarate is the obligatory substrate of 2-OGDO enzymes, whereas succinate and fumarate are the inhibitors of these enzymes. Moreover, citrate can stimulate histone acetylation via acetyl-CoA production. Epigenetic studies have revealed that AD is associated with changes in DNA methylation and histone acetylation patterns. However, the epigenetic results of different studies are inconsistent but one possibility is that they represent both coordinated adaptive responses and uncontrolled stochastic changes, which provoke pathogenesis in affected neurons. Here, we will review the changes observed in mitochondrial dynamics and Krebs cycle function associated with AD, and then clarify the mechanisms through which mitochondrial metabolites can control the epigenetic landscape of chromatin and induce pathological changes in AD.

  15. Analysis of Mitochondrial Proteins in the Surviving Myocardium after Ischemia Identifies Mitochondrial Pyruvate Carrier Expression as Possible Mediator of Tissue Viability.

    Science.gov (United States)

    Fernández-Caggiano, Mariana; Prysyazhna, Oleksandra; Barallobre-Barreiro, Javier; CalviñoSantos, Ramón; Aldama López, Guillermo; Generosa Crespo-Leiro, Maria; Eaton, Philip; Doménech, Nieves

    2016-01-01

    The endogenous mechanisms contributing to tissue survival following myocardial infarction are not fully understood. We investigated the alterations in the mitochondrial proteome after ischemia-reperfusion (I/R) and its possible implications on cell survival. Mitochondrial proteomic analysis of cardiac tissue from an in vivo porcine I/R model found that surviving tissue in the peri-infarct border zone showed increased expression of several proteins. Notably, these included subunits of the mitochondrial pyruvate carrier (MPC), namely MPC1 and MPC2. Western blot, immunohistochemistry, and mRNA analysis corroborated the elevated expression of MPC in the surviving tissue. Furthermore, MPC1 and MPC2 protein levels were found to be markedly elevated in the myocardium of ischemic cardiomyopathy patients. These findings led to the hypothesis that increased MPC expression is cardioprotective due to enhancement of mitochondrial pyruvate uptake in the energy-starved heart following I/R. To test this, isolated mouse hearts perfused with a modified Krebs buffer (containing glucose, pyruvate, and octanoate as metabolic substrates) were subjected to I/R with or without the MPC transport inhibitor UK5099. UK5099 increased myocardial infarction and attenuated post-ischemic recovery of left ventricular end-diastolic pressure. However, aerobically perfused control hearts that were exposed to UK5099 did not modulate contractile function, although pyruvate uptake was blocked as evidenced by increased cytosolic lactate and pyruvate levels. Our findings indicate that increased expression of MPC leads to enhanced uptake and utilization of pyruvate during I/R. We propose this as a putative endogenous mechanism that promotes myocardial survival to limit infarct size.

  16. Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes.

    Science.gov (United States)

    Wada, Jun; Nakatsuka, Atsuko

    2016-06-01

    The mitochondria are involved in active and dynamic processes, such as mitochondrial biogenesis, fission, fusion and mitophagy to maintain mitochondrial and cellular functions. In obesity and type 2 diabetes, impaired oxidation, reduced mitochondrial contents, lowered rates of oxidative phosphorylation and excessive reactive oxygen species (ROS) production have been reported. Mitochondrial biogenesis is regulated by various transcription factors such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and nuclear respiratory factors (NRFs). Mitochondrial fusion is promoted by mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy 1 (OPA1), while fission is governed by the recruitment of dynamin-related protein 1 (DRP1) by adaptor proteins such as mitochondrial fission factor (MFF), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51), and fission 1 (FIS1). Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARKIN promote DRP1-dependent mitochondrial fission, and the outer mitochondrial adaptor MiD51 is required in DRP1 recruitment and PARKIN-dependent mitophagy. This review describes the molecular mechanism of mitochondrial dynamics, its abnormality in diabetes and obesity, and pharmaceuticals targeting mitochondrial biogenesis, fission, fusion and mitophagy. PMID:27339203

  17. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus;

    2014-01-01

    and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  18. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

    Directory of Open Access Journals (Sweden)

    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  19. Low-cost step aerobics system with virtual aerobics trainer

    OpenAIRE

    Rosa, Alejandro; Barbancho, Isabel; Tardón, Lorenzo J.; Barbancho, Ana M.

    2014-01-01

    In this paper a low-cost step-aerobics instructor simulation system is presented. The proposed system analyses a given song to iden- tify its rhythmic pattern. Subsequently, this rhythmic pattern is used in order to issue a set of steps-aerobics commands to the user, thus simu- lating a training session. The system uses a Wii Balance Board to track exercises performed by users and runs on an Android smartphone. A set of tests were conducted to assess user experience and opin...

  20. Nanodelivery System for Mitochondrial Targeting

    Science.gov (United States)

    Yoong, Sia Lee; Pastorin, Giorgia

    2014-02-01

    Mitochondria are indispensable in cellular functions such as energy production and death execution. They are emerging as intriguing therapeutic target as their dysregulation was found to be monumental in diseases such as neurodegenerative disease, obesity, and cancer etc. Despite tremendous interest being focused on therapeutically intervening mitochondrial function, few mito-active drugs were successfully developed, particularly due to challenges in delivering active compound to this organelle. In this review, effort in utilizing nanotechnology for targeted mitochondrial delivery of compound is expounded based on the nature of the nanomaterial used. The advantage and potential offered are discussed alongside the limitation. Finally the review is concluded with perspectives of the application of nanocarrier in mitochondrial medicine, given the unresolved concern on potential complications.

  1. Exercise intensity during Zumba fitness and Tae-bo aerobics

    OpenAIRE

    Hižnayová, Kristína

    2013-01-01

    This study analyzed and compared the exercise intensity in Zumba fitness and Tae-bo aerobics. Object of the research was monitoring of the heart rate and energy consumption in kcal during exercise unit, by using Heart Rate Monitor Suunto Memory Belt. All measurements were attended by randomly selected 11 women. The data we collected during the six units of the Zumba fitness and six units of the Tae-bo aerobics . Obtained data of the heart rate were evaluated in three main parts of workout: af...

  2. VDAC electronics: 1. VDAC-hexo(gluco)kinase generator of the mitochondrial outer membrane potential.

    Science.gov (United States)

    Lemeshko, Victor V

    2014-05-01

    The simplest mechanism of the generation of the mitochondrial outer membrane potential (OMP) by the VDAC (voltage-dependent anion channel)-hexokinase complex (VHC), suggested earlier, and by the VDAC-glucokinase complex (VGC), was computationally analyzed. Even at less than 4% of VDACs bound to hexokinase, the calculated OMP is high enough to trigger the electrical closure of VDACs beyond the complexes at threshold concentrations of glucose. These results confirmed our previous hypothesis that the Warburg effect is caused by the electrical closure of VDACs, leading to global restriction of the outer membrane permeability coupled to aerobic glycolysis. The model showed that the inhibition of the conductance and/or an increase in the voltage sensitivity of a relatively small fraction of VDACs by factors like tubulin potentiate the electrical closure of the remaining free VDACs. The extrusion of calcium ions from the mitochondrial intermembrane space by the generated OMP, positive inside, might increase cancer cell resistance to death. Within the VGC model, the known effect of induction of ATP release from mitochondria by accumulated glucose-6-phosphate in pancreatic beta cells might result not only of the known effect of GK dissociation from the VDAC-GK complex, but also of a decrease in the free energy of glucokinase reaction, leading to the OMP decrease and VDAC opening. We suggest that the VDAC-mediated electrical control of the mitochondrial outer membrane permeability, dependent on metabolic conditions, is a fundamental physiological mechanism of global regulation of mitochondrial functions and of cell death. PMID:24412217

  3. Non-cytotoxic copper overload boosts mitochondrial energy metabolism to modulate cell proliferation and differentiation in the human erythroleukemic cell line K562.

    Science.gov (United States)

    Ruiz, Lina M; Jensen, Erik L; Rossel, Yancing; Puas, German I; Gonzalez-Ibanez, Alvaro M; Bustos, Rodrigo I; Ferrick, David A; Elorza, Alvaro A

    2016-07-01

    Copper is integral to the mitochondrial respiratory complex IV and contributes to proliferation and differentiation, metabolic reprogramming and mitochondrial function. The K562 cell line was exposed to a non-cytotoxic copper overload to evaluate mitochondrial dynamics, function and cell fate. This induced higher rates of mitochondrial turnover given by an increase in mitochondrial fusion and fission events and in the autophagic flux. The appearance of smaller and condensed mitochondria was also observed. Bioenergetics activity included more respiratory complexes, higher oxygen consumption rate, superoxide production and ATP synthesis, with no decrease in membrane potential. Increased cell proliferation and inhibited differentiation also occurred. Non-cytotoxic copper levels can modify mitochondrial metabolism and cell fate, which could be used in cancer biology and regenerative medicine. PMID:27094959

  4. Isolation and denitrification characteristic of an aerobic denitrifier

    Institute of Scientific and Technical Information of China (English)

    ZHOU Dan-dan; MA Fang; WANG Hong-yu; DONG Shuang-shi; WANG Ai-jie

    2006-01-01

    Aerobic denitrifiers were enriched by activated sludge cultivation method. By this way, 105 strains were isolated from the activated sludge and 25 strains were confirmed to be capable of obtaining energy by deoxidization of nitrate to nitrogen gas under aerobic condition. The characteristic of one denitrifier, Pseudomonas chloritidismutans strain, was particularly studied due to its higher nitrogen removal rate. It was found that Pseudomonas chloritidismutans can use nitrite, nitrate and oxygen for aerobic respiration in liquid medium, and the pH increased and ORP decreased by activated denitrifier. When they used nitrite or nitrate for respiration, nitrogen removal effect was high and nitrite could be reduced more efficiently than nitrate. Denitrification process was accomplished faster when both nitrite and nitrate existed in the medium compared to each of which existed alone. Particularly, at denitrifying activity, the nitrogen removal rate of strain was not affected by the DO concentration in the culture media.

  5. Aerobic exercise in pulmonary rehabilitation

    Directory of Open Access Journals (Sweden)

    Thiago Brasileiro de Vasconcelos

    2013-01-01

    Full Text Available The aim of this study was to conduct a literature review on the usefulness of aerobic exercise in pulmonary rehabilitation. This is an exploratory study of literature through the electronic databases Medline, Lilacs, Scielo, Pubmed and Google Scholar, published between 1996 and 2012, conducted during the period February to May 2012 with the following keywords: COPD, pulmonary rehabilitation, aerobic exercises, physical training, quality of life. The change in pulmonary function and dysfunction of skeletal muscles that result in exercise intolerance and reduced fitness and may cause social isolation, depression, anxiety and addiction. The training exercise is the most important component of the program of pulmonary rehabilitation where the aerobic training provides consistent results in clinical improvement in levels of exercise tolerance and decreased dyspnea generating more benefits to the body, reducing the chance of cardiovascular disease and improves quality and expectation of life. We demonstrated that the use of aerobic exercise in pulmonary rehabilitation program, allows an improvement of motor skills, decreased muscle fatigue and deconditioning, reducing sedentary lifestyle; however, has little or no effect on the reduction of strength and atrophy muscle.

  6. Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming.

    Science.gov (United States)

    Buck, Michael D; O'Sullivan, David; Klein Geltink, Ramon I; Curtis, Jonathan D; Chang, Chih-Hao; Sanin, David E; Qiu, Jing; Kretz, Oliver; Braas, Daniel; van der Windt, Gerritje J W; Chen, Qiongyu; Huang, Stanley Ching-Cheng; O'Neill, Christina M; Edelson, Brian T; Pearce, Edward J; Sesaki, Hiromi; Huber, Tobias B; Rambold, Angelika S; Pearce, Erika L

    2016-06-30

    Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, by altering cristae morphology, fusion in TM cells configures electron transport chain (ETC) complex associations favoring oxidative phosphorylation (OXPHOS) and FAO, while fission in TE cells leads to cristae expansion, reducing ETC efficiency and promoting aerobic glycolysis. Thus, mitochondrial remodeling is a signaling mechanism that instructs T cell metabolic programming. PMID:27293185

  7. Polychlorinated Biphenyls Induce Mitochondrial Dysfunction in SH-SY5Y Neuroblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Stefania Cocco

    Full Text Available Chronic exposure to polychlorinated biphenyls (PCBs, ubiquitous environmental contaminants, can adversely affect the development and function of the nervous system. Here we evaluated the effect of PCB exposure on mitochondrial function using the PCB mixture Aroclor-1254 (A1254 in SH-SY5Y neuroblastoma cells. A 6-hour exposure to A1254 (5 μg/ml reduced cellular ATP production by 45%±7, and mitochondrial membrane potential, detected by TMRE, by 49%±7. Consistently, A1254 significantly decreased oxidative phosphorylation and aerobic glycolysis measured by extracellular flux analyzer. Furthermore, the activity of mitochondrial protein complexes I, II, and IV, but not V (ATPase, measured by BN-PAGE technique, was significantly reduced after 6-hour exposure to A1254. The addition of pyruvic acid during exposure to A1254 significantly prevent A1254-induced cell injury, restoring resting mitochondrial membrane potential, ATP levels, oxidative phosphorylation and aerobic glycolysis. Furthermore, pyruvic acid significantly preserved the activity of mitochondrial complexes I, II and IV and increased basal activity of complex V. Collectively, the present results indicate that the neurotoxicity of A1254 depends on the impairment of oxidative phosphorylation, aerobic glycolysis, and mitochondrial complexes I, II, and IV activity and it was counteracted by pyruvic acid.

  8. 两种供能方式对厨余垃圾好氧堆肥的影响研究%EFFECT OF TWO METHODS OF ENERGY SUPPLY ON AEROBIC COMPOSTING OF THE KITCHEN GARBAGE

    Institute of Scientific and Technical Information of China (English)

    李兵; 董志颖; 王英

    2012-01-01

    为了探索厨余垃圾堆肥过程中物料保持高温的方式,分别设置壁管式和水浴式供能好氧堆肥装置。实验结果表明:堆肥5 d后水浴式供能堆肥装置堆体内部的温度高于壁管式装置,且维持45℃以上范围长达8 d;两者堆肥周期都为13 d;实验结束时,水浴式供能堆肥装置内物料pH为8.7,高于壁管式装置的8.3。水浴式供能堆肥装置内物料的C/N值、BDM分别为9.2和18.1%,低于壁管式装置的9.2和30.0%。两种供能方式均能使厨余垃圾在极短时间内达到稳定化。%In order to study how to keep high temperature during aerobic composting of the kitchen garbage,two aerobic composting equipments with energy supply through water bath and tubes respectively were used in the experiment,whose interval was 13 d.Results showed the two equipments could keep temperature of garbage higher than 45 ℃ for 8 d and the temperature in equipment with water bath was always higher than that in equipment with tubes after 5 d.When the experiment was finished,C/N,BDM and pH of the inner meterial in the equipment with water bath were 9.2,18.1% and 8.7;C/N,BDM and pH of the material in the equipment with tubes were 9.2,30% and 8.3.Therefore,the two equipments could make kitchen garbage reach stabilization in very short time.

  9. Parkin suppresses Drp1-independent mitochondrial division.

    Science.gov (United States)

    Roy, Madhuparna; Itoh, Kie; Iijima, Miho; Sesaki, Hiromi

    2016-07-01

    The cycle of mitochondrial division and fusion disconnect and reconnect individual mitochondria in cells to remodel this energy-producing organelle. Although dynamin-related protein 1 (Drp1) plays a major role in mitochondrial division in cells, a reduced level of mitochondrial division still persists even in the absence of Drp1. It is unknown how much Drp1-mediated mitochondrial division accounts for the connectivity of mitochondria. The role of a Parkinson's disease-associated protein-parkin, which biochemically and genetically interacts with Drp1-in mitochondrial connectivity also remains poorly understood. Here, we quantified the number and connectivity of mitochondria using mitochondria-targeted photoactivatable GFP in cells. We show that the loss of Drp1 increases the connectivity of mitochondria by 15-fold in mouse embryonic fibroblasts (MEFs). While a single loss of parkin does not affect the connectivity of mitochondria, the connectivity of mitochondria significantly decreased compared with a single loss of Drp1 when parkin was lost in the absence of Drp1. Furthermore, the loss of parkin decreased the frequency of depolarization of the mitochondrial inner membrane that is caused by increased mitochondrial connectivity in Drp1-knockout MEFs. Therefore, our data suggest that parkin negatively regulates Drp1-indendent mitochondrial division.

  10. Parkin suppresses Drp1-independent mitochondrial division.

    Science.gov (United States)

    Roy, Madhuparna; Itoh, Kie; Iijima, Miho; Sesaki, Hiromi

    2016-07-01

    The cycle of mitochondrial division and fusion disconnect and reconnect individual mitochondria in cells to remodel this energy-producing organelle. Although dynamin-related protein 1 (Drp1) plays a major role in mitochondrial division in cells, a reduced level of mitochondrial division still persists even in the absence of Drp1. It is unknown how much Drp1-mediated mitochondrial division accounts for the connectivity of mitochondria. The role of a Parkinson's disease-associated protein-parkin, which biochemically and genetically interacts with Drp1-in mitochondrial connectivity also remains poorly understood. Here, we quantified the number and connectivity of mitochondria using mitochondria-targeted photoactivatable GFP in cells. We show that the loss of Drp1 increases the connectivity of mitochondria by 15-fold in mouse embryonic fibroblasts (MEFs). While a single loss of parkin does not affect the connectivity of mitochondria, the connectivity of mitochondria significantly decreased compared with a single loss of Drp1 when parkin was lost in the absence of Drp1. Furthermore, the loss of parkin decreased the frequency of depolarization of the mitochondrial inner membrane that is caused by increased mitochondrial connectivity in Drp1-knockout MEFs. Therefore, our data suggest that parkin negatively regulates Drp1-indendent mitochondrial division. PMID:27181353

  11. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression.

    Science.gov (United States)

    Jourdain, Alexis A; Boehm, Erik; Maundrell, Kinsey; Martinou, Jean-Claude

    2016-03-14

    In mitochondria, DNA replication, gene expression, and RNA degradation machineries coexist within a common nondelimited space, raising the question of how functional compartmentalization of gene expression is achieved. Here, we discuss the recently characterized "mitochondrial RNA granules," mitochondrial subdomains with an emerging role in the regulation of gene expression. PMID:26953349

  12. Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells through both of the mitochondrial respiration and glycolysis pathways.

    Directory of Open Access Journals (Sweden)

    Yao Shen

    Full Text Available Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy.

  13. Miro, MCU, and calcium: bridging our understanding of mitochondrial movement in axons

    Directory of Open Access Journals (Sweden)

    Robert eNiescier

    2013-09-01

    Full Text Available Neurons are extremely polarized structures with long axons and dendrites, which require proper distribution of mitochondria and maintenance of mitochondrial dynamics for neuronal functions and survival. Indeed, recent studies show that various neurological disorders are linked to mitochondrial transport in neurons. Mitochondrial anterograde transport is believed to deliver metabolic energy to synaptic terminals where energy demands are high, while mitochondrial retrograde transport is required to repair or remove damaged mitochondria in axons. It has been suggested that Ca2+ plays a key role in regulating mitochondrial transport by altering the configuration of mitochondrial protein, miro. However, molecular mechanisms that regulate mitochondrial transport in neurons still are not well characterized. In this review, we will discuss the roles of miro in mitochondrial transport and how the recently identified components of the mitochondrial calcium uniporter add to our current model of mitochondrial mobility regulation.

  14. Miro, MCU, and calcium: bridging our understanding of mitochondrial movement in axons.

    Science.gov (United States)

    Niescier, Robert F; Chang, Karen T; Min, Kyung-Tai

    2013-09-10

    Neurons are extremely polarized structures with long axons and dendrites, which require proper distribution of mitochondria and maintenance of mitochondrial dynamics for neuronal functions and survival. Indeed, recent studies show that various neurological disorders are linked to mitochondrial transport in neurons. Mitochondrial anterograde transport is believed to deliver metabolic energy to synaptic terminals where energy demands are high, while mitochondrial retrograde transport is required to repair or remove damaged mitochondria in axons. It has been suggested that Ca(2) (+) plays a key role in regulating mitochondrial transport by altering the configuration of mitochondrial protein, miro. However, molecular mechanisms that regulate mitochondrial transport in neurons still are not well characterized. In this review, we will discuss the roles of miro in mitochondrial transport and how the recently identified components of the mitochondrial calcium uniporter add to our current model of mitochondrial mobility regulation.

  15. Grey water treatment in a series anaerobic--aerobic system for irrigation.

    Science.gov (United States)

    Abu Ghunmi, Lina; Zeeman, Grietje; Fayyad, Manar; van Lier, Jules B

    2010-01-01

    This study aims at treatment of grey water for irrigation, focusing on a treatment technology that is robust, simple to operate and with minimum energy consumption. The result is an optimized system consisting of an anaerobic unit operated in upflow mode, with a 1 day operational cycle, a constant effluent flow rate and varying liquid volume. Subsequent aerobic step is equipped with mechanical aeration and the system is insulated for sustaining winter conditions. The COD removal achieved by the anaerobic and aerobic units in summer and winter are 45%, 39% and 53%, 64%, respectively. Sludge in the anaerobic and aerobic reactor has a concentration of 168 and 8 mg VSL(-1), respectively. Stability of sludge in the anaerobic and aerobic reactors is 80% and 93%, respectively, based on COD. Aerobic effluent quality, except for pathogens, agrees with the proposed irrigation water quality guidelines for reclaimed water in Jordan. PMID:19699088

  16. Mitochondrial targeted β-lapachone induces mitochondrial dysfunction and catastrophic vacuolization in cancer cells.

    Science.gov (United States)

    Ma, Jing; Lim, Chaemin; Sacher, Joshua R; Van Houten, Bennett; Qian, Wei; Wipf, Peter

    2015-11-01

    Mitochondria play important roles in tumor cell physiology and survival by providing energy and metabolites for proliferation and metastasis. As part of their oncogenic status, cancer cells frequently produce increased levels of mitochondrial-generated reactive oxygen species (ROS). However, extensive stimulation of ROS generation in mitochondria has been shown to be able to induce cancer cell death, and is one of the major mechanisms of action of many anticancer agents. We hypothesized that enhancing mitochondrial ROS generation through direct targeting of a ROS generator into mitochondria will exhibit tumor cell selectivity, as well as high efficacy in inducing cancer cell death. We thus synthesized a mitochondrial targeted version of β-lapachone (XJB-Lapachone) based on our XJB mitochondrial targeting platform. We found that the mitochondrial targeted β-lapachone is more efficient in inducing apoptosis compared to unconjugated β-lapachone, and the tumor cell selectivity is maintained. XJB-Lapachone also induced extensive cellular vacuolization and autophagy at a concentration not observed with unconjugated β-lapachone. Through characterization of mitochondrial function we revealed that XJB-Lapachone is indeed more capable of stimulating ROS generation in mitochondria, which led to a dramatic mitochondrial uncoupling and autophagic degradation of mitochondria. Taken together, we have demonstrated that targeting β-lapachone accomplishes higher efficacy through inducing ROS generation directly in mitochondria, resulting in extensive mitochondrial and cellular damage. XJB-Lapachone will thus help to establish a novel platform for the design of next generation mitochondrial targeted ROS generators for cancer therapy.

  17. Aerobic microbial enhanced oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Torsvik, T. [Univ. of Bergen (Norway); Gilje, E.; Sunde, E.

    1995-12-31

    In aerobic MEOR, the ability of oil-degrading bacteria to mobilize oil is used to increase oil recovery. In this process, oxygen and mineral nutrients are injected into the oil reservoir in order to stimulate growth of aerobic oil-degrading bacteria in the reservoir. Experiments carried out in a model sandstone with stock tank oil and bacteria isolated from offshore wells showed that residual oil saturation was lowered from 27% to 3%. The process was time dependent, not pore volume dependent. During MEOR flooding, the relative permeability of water was lowered. Oxygen and active bacteria were needed for the process to take place. Maximum efficiency was reached at low oxygen concentrations, approximately 1 mg O{sub 2}/liter.

  18. Strokes in mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    N V Pizova

    2012-01-01

    Full Text Available It is suggested that mitochondrial diseases might be identified in 22—33% of cryptogenic stroke cases in young subjects. The incidence of mitochondrial disorders in patients with stroke is unknown; it is 0.8 to 7.2% according to the data of some authors. The paper gives data on the prevalence, pathogenesis, and clinical manifestations of mitochondrial diseases, such as mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS and insulin-like episodes; myoclonic epilepsy and ragged-red fibers (MERRF syndrome, and Kearns-Sayre syndrome (sporadic multisystem mitochondrial pathology.

  19. Beneifcial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Rui Guo; Emily C Liong; Kwok Fai So; Man-Lung Fung; George L Tipoe

    2015-01-01

    BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneifcial effects of aerobic exercise on NAFLD. DATA SOURCE:We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. RESULTS:The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing in-trahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptorγ expression levels; (ii) decreas-ing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inlfammation via the inhibition of pro-inlfammatory media-tors such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. CONCLUSION:Aerobic exercise, via different mechanisms, signiifcantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

  20. Evidence of mitochondrial dysfunction in obese adolescents

    DEFF Research Database (Denmark)

    Wilms, L; Larsen, J; Pedersen, P L;

    2010-01-01

    Abstract Aim: Although obesity and weight gain generally are anticipated to be caused by an imbalance between energy intake and energy expenditure, the significance of thyroid hormones (TH) remains unclear. Examination of mitochondrial function may reflect intracellular thyroid hormone effect...... and mitochondrial function in peripheral blood monocytes was determined by flow cytometry. Results: Significant increase in TSH (3.06 +/- 1.56 mU/L vs. 2.33 +/- 0.91 mU/L, p ... compared with lean adolescents. Flow cytometry analysis demonstrated a lower mitochondrial mass (6385 +/- 1962 a.u. vs. 7608 +/- 2328 a.u., p mitochondrial membrane potential (11426 +/- 3861 a.u. vs. 14017 +/- 5536 a.u., p

  1. Aerobic conditioning for team sport athletes.

    Science.gov (United States)

    Stone, Nicholas M; Kilding, Andrew E

    2009-01-01

    Team sport athletes require a high level of aerobic fitness in order to generate and maintain power output during repeated high-intensity efforts and to recover. Research to date suggests that these components can be increased by regularly performing aerobic conditioning. Traditional aerobic conditioning, with minimal changes of direction and no skill component, has been demonstrated to effectively increase aerobic function within a 4- to 10-week period in team sport players. More importantly, traditional aerobic conditioning methods have been shown to increase team sport performance substantially. Many team sports require the upkeep of both aerobic fitness and sport-specific skills during a lengthy competitive season. Classic team sport trainings have been shown to evoke marginal increases/decreases in aerobic fitness. In recent years, aerobic conditioning methods have been designed to allow adequate intensities to be achieved to induce improvements in aerobic fitness whilst incorporating movement-specific and skill-specific tasks, e.g. small-sided games and dribbling circuits. Such 'sport-specific' conditioning methods have been demonstrated to promote increases in aerobic fitness, though careful consideration of player skill levels, current fitness, player numbers, field dimensions, game rules and availability of player encouragement is required. Whilst different conditioning methods appear equivalent in their ability to improve fitness, whether sport-specific conditioning is superior to other methods at improving actual game performance statistics requires further research.

  2. Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using polarography and spectrophotometric enzyme assays.

    Science.gov (United States)

    Barrientos, Antoni; Fontanesi, Flavia; Díaz, Francisca

    2009-10-01

    The oxidative phosphorylation (OXPHOS) system consists of five multimeric complexes embedded in the mitochondrial inner membrane. They work in concert to drive the aerobic synthesis of ATP. Mitochondrial and nuclear DNA mutations affecting the accumulation and function of these enzymes are the most common cause of mitochondrial diseases and have also been associated with neurodegeneration and aging. For this reason, several approaches for the assessment of the OXPHOS system enzymes have been developed. Based on the methods described elsewhere, the assays describe methods that form a biochemical characterization of the OXPHOS system in cells and mitochondria isolated from cultured cells or tissues.

  3. Gasto energético aeróbico y anaeróbico en un circuito con cargas a seis intensidades diferentes. (Aerobic and anaerobic energy expenditure during at circuit weight training through six different intensities.

    Directory of Open Access Journals (Sweden)

    Rocío Cupeiro Coto

    2011-07-01

    Full Text Available ResumenEl entrenamiento con cargas es una actividad anaeróbica glucolítica intensa y se ha comprobado que el error en las estimaciones del gasto energético en esta actividad varía entre un 13 y un 30%. El principal objetivo de este trabajo es describir la contribución anaeróbica de energía en un circuito con cargas. Doce hombres (20-26 años y diecisiete mujeres (18-29 años estudiantes de Ciencias de la Actividad Física y del Deporte realizaron un entrenamiento en circuito de cargas a 6 intensidades diferentes (entre el 30% y 80% de su 15RM. Durante la totalidad de los circuitos se registró el gasto energético aeróbico por calorimetría indirecta, la frecuencia cardiaca con pulsómetro Polar® y la concentración de lactato en sangre capilar para medir la contribución anaeróbica. El incremento que produjo la energía anaeróbica se situó entre el 5,1% y un máximo del 13,5%, lo que hace evidente que medir o no la contribución anaeróbica en el entrenamiento en circuito puede provocar un error medio del 9,65%. Existen diferencias significativas (PAbstractResistance training is an intense anaerobic glycolytic activity and has been shown that estimates of energy expenditure in this activity turn out into an error that varies between 13 and 30%. The main aim of this paper is to describe the anaerobic energy contribution in circuit weight training. Twelve men (20-26 years and seventeen women (18-29 years students in Science of Physical Activity and Sport performed circuit training at six different intensities (between 30% and 80% of 15RM. During all the circuits aerobic energy expenditure was registered by indirect calorimetry, heart rate with Polar® monitors and lactate concentration in capillary blood to measure the anaerobic contribution. The increased due to anaerobic energy was between 5,1% and a maximum of 13,5%, which clearly means that to measure or not the anaerobic contribution in circuit training can lead to an average

  4. Personality, metabolic rate and aerobic capacity.

    Directory of Open Access Journals (Sweden)

    Antonio Terracciano

    Full Text Available Personality traits and cardiorespiratory fitness in older adults are reliable predictors of health and longevity. We examined the association between personality traits and energy expenditure at rest (basal metabolic rate and during normal and maximal sustained walking. Personality traits and oxygen (VO(2 consumption were assessed in 642 participants from the Baltimore Longitudinal Study of Aging. Results indicate that personality traits were mostly unrelated to resting metabolic rate and energy expenditure at normal walking pace. However, those who scored lower on neuroticism (r = -0.12 and higher on extraversion (r = 0.11, openness (r = 0.13, and conscientiousness (r = 0.09 had significantly higher energy expenditure at peak walking pace. In addition to greater aerobic capacity, individuals with a more resilient personality profile walked faster and were more efficient in that they required less energy per meter walked. The associations between personality and energy expenditure were not moderated by age or sex, but were in part explained by the proportion of fat mass. In conclusion, differences in personality may matter the most during more challenging activities that require cardiorespiratory fitness. These findings suggest potential pathways that link personality to health outcomes, such as obesity and longevity.

  5. A mitochondrial alkaline/neutral invertase isoform (A/N-InvC) functions in developmental energy-demanding processes in Arabidopsis.

    Science.gov (United States)

    Martín, Mariana L; Lechner, Leandra; Zabaleta, Eduardo J; Salerno, Graciela L

    2013-03-01

    Recent findings demonstrate that alkaline/neutral invertases (A/N-Invs), enzymes that catalyze the breakdown of sucrose into glucose and fructose, are essential proteins in plant life. The fact that different isoforms are present in multiple locations makes them candidates for the coordination of metabolic processes. In the present study, we functionally characterized the encoding gene of a novel A/N-Inv (named A/N-InvC) from Arabidopsis, which localizes in mitochondria. A/N-InvC is expressed in roots, in aerial parts (shoots and leaves) and flowers. A detailed phenotypic analysis of knockout mutant plants (invc) reveals an impaired growth phenotype. Shoot growth was severely reduced, but root development was not affected as reported for A/N-InvA mutant (inva) plants. Remarkably, germination and flowering, two energy demanding processes, were the most affected stages. The effect of exogenous growth regulators led us to suggest that A/N-InvC may be modulating hormone balance in relation to the radicle emergence. We also show that oxygen consumption is reduced in inva and invc in comparison with wild-type plants, indicating that both organelle isoenzymes may play a fundamental role in mitochondrion functionality. Taken together, our results emphasize the involvement of mitochondrial A/N-Invs in developmental processes and uncover the possibility of playing different roles for the two isoforms located in the organelle.

  6. Molecular structure and pathophysiological roles of the Mitochondrial Calcium Uniporter.

    Science.gov (United States)

    Mammucari, Cristina; Raffaello, Anna; Vecellio Reane, Denis; Rizzuto, Rosario

    2016-10-01

    Mitochondrial Ca(2+) uptake regulates a wide array of cell functions, from stimulation of aerobic metabolism and ATP production in physiological settings, to induction of cell death in pathological conditions. The molecular identity of the Mitochondrial Calcium Uniporter (MCU), the highly selective channel responsible for Ca(2+) entry through the IMM, has been described less than five years ago. Since then, research has been conducted to clarify the modulation of its activity, which relies on the dynamic interaction with regulatory proteins, and its contribution to the pathophysiology of organs and tissues. Particular attention has been placed on characterizing the role of MCU in cardiac and skeletal muscles. In this review we summarize the molecular structure and regulation of the MCU complex in addition to its pathophysiological role, with particular attention to striated muscle tissues. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:26968367

  7. Estrogen regulation of mitochondrial bioenergetics: implications for prevention of Alzheimer's disease.

    Science.gov (United States)

    Yao, Jia; Brinton, Roberta Diaz

    2012-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised aerobic glycolysis pathway coupled with oxidative stress is first accompanied by a shift toward a ketogenic pathway that eventually progresses into fatty acid oxidation (FAO) pathways and leads to white matter degeneration and overproduction and mitochondrial accumulation of β-amyloid. Estrogen-induced signaling pathways converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis coupled with citric acid cycle-driven oxidative phosphorylation to potentiate ATP (Adenosine triphosphate) generation. In addition to potentiated mitochondrial bioenergetics, estrogen also enhances neural survival and health through maintenance of calcium homeostasis, promotion of antioxidant defense against free radicals, efficient cholesterol trafficking, and beta amyloid clearance. Significantly, the convergence of E2 mechanisms of action onto mitochondria is also a potential point of vulnerability when activated in diseased neurons that exacerbates degeneration through increased load on dysregulated calcium homeostasis. The "healthy cell bias of estrogen action" hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. As the continuum of neurological health progresses from healthy to unhealthy, so too do the benefits of estrogen or hormone therapy.

  8. Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Justin D Crane

    Full Text Available Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2 (+/- mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2 (+/- mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2 (+/- mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity.

  9. Mitochondrial plasticity in pathophysiological conditions

    OpenAIRE

    Padrão, Ana Isabel Martins Novais

    2013-01-01

    Both skeletal and cardiac muscles daily burn tremendous amounts of ATP to meet the energy requirements for contraction. So, it is not surprising that the maintenance of mitochondrial morphology, number, distribution and functionality in striated muscle are important for muscle homeostasis. In these tissues mitochondria present the added dimension of two populations, the intermyofibrillar (IMF) and the subsarcolemmal (SS) mitochondria, being IMF the most abundant one. In the present thesis, th...

  10. The Lomagundi Event Marks Post-Pasteur Point Evolution of Aerobic Respiration: A Hypothesis

    Science.gov (United States)

    Raub, T. D.; Kirschvink, J. L.; Nash, C. Z.; Raub, T. M.; Kopp, R. E.; Hilburn, I. A.

    2009-05-01

    All published early Earth carbon cycle models assume that aerobic respiration is as ancient as oxygenic photosynthesis. However, aerobic respiration shuts down at oxygen concentrations below the Pasteur Point, (.01 of the present atmospheric level, PAL). As geochemical processes are unable to produce even local oxygen concentrations above .001 PAL, it follows that aerobic respiration could only have evolved after oxygenic photosynthesis, implying a time gap. The evolution of oxygen reductase-utilizing metabolisms presumably would have occupied this interval. During this time the PS-II-generated free oxygen would have been largely unavailable for remineralization of dissolved organic carbon and so would have profoundly shifted the burial ratio of organic/inorganic carbon. We argue that the sequential geological record of the Makganyene (Snowball?) glaciation (2.3-2.22), the exessively aerobic Hekpoort and coeval paleosols, the Lomagundi-Jatuli carbon isotopic excursion (ending 2.056 Ga), and the deposition of concentrated, sedimentary organic carbon (shungite) mark this period of a profoundly unbalanced global carbon cycle. The Kopp et al. (2005) model for oxyatmoversion agrees with phylogenetic evidence for the radiation of cyanobacteria followed closely by the radiation of gram-negative lineages containing magnetotactic bacteria, which depend upon vertical oxygen gradients. These organisms include delta-Proteobacteria from which the mitochondrial ancestor originated. The Precambrian carbon cycle was rebalanced after a series of biological innovations allowed utilization of the high redox potential of free oxygen. Aerobic respiration in mitochondria required the evolution of a unique family of Fe-Cu oxidases, one of many factors contributing to the >210 Myr delay between the Makganyene deglaciation and the end of the Lomagundi-Jatuli event. We speculate that metalliferious fluids associated with the eruption of the Bushveld complex facilitated evolution of these

  11. Mitochondrial Composition,Function and Stress Response in Plants

    Institute of Scientific and Technical Information of China (English)

    Richard P.Jacoby; Lei Li; Shaobai Huang; Chun Pong Lee; A.Harvey Millar; Nicolas L.Taylor

    2012-01-01

    The primary function of mitochondria is respiration,where catabolism of substrates is coupled to ATP synthesis via oxidative phosphorylation.In plants,mitochondrial composition is relatively complex and flexible and has specific pathways to support photosynthetic processes in illuminated leaves.This review begins with outlining current models of mitochondrial composition in plant cells,with an emphasis upon the assembly of the complexes of the classical electron transport chain (ETC).Next,we focus upon the comparative analysis of mitochondrial function from different tissue types.A prominent theme in the plant mitochondrial literature involves linking mitochondrial composition to environmental stress responses,and this review then gives a detailed outline of how oxidative stress impacts upon the plant mitochondrial proteome with particular attention to the role of transition metals.This is followed by an analysis of the signaling capacity of mitochondrial reactive oxygen species,which studies the transcriptional changes of stress responsive genes as a framework to define specific signals emanating from the mitochondrion.Finally,specific mitochondrial roles during exposure to harsh environments are outlined,with attention paid to mitochondrial delivery of energy and intermediates,mitochondrial support for photosynthesis,and mitochondrial processes operating within root cells that mediate tolerance to anoxia and unfavorable soil chemistries.

  12. Ketogenesis in isolated rat liver mitochondria I. Relationships with the citric acid cycle and with the mitochondrial energy state

    NARCIS (Netherlands)

    Lopes-Cardozo, M.; Bergh, S.G. van den

    1972-01-01

    1. A method is described to calculate the distribution of acetyl-CoA over the citric acid cycle and ketogenesis during the oxidation of fatty acids in the presence of added malate. 2. Increasing concentrations of added Krebs cycle intermediates lower the rate of ketogenesis both in the low-energy s

  13. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  14. Pathological Mutations of the Mitochondrial Human Genome: the Instrumental Role of the Yeast S. cerevisiae

    Directory of Open Access Journals (Sweden)

    Monique Bolotin-Fukuhara

    2014-01-01

    Full Text Available Mitochondrial diseases, which altogether represent not so rare diseases, can be due to mutations either in the nuclear or mitochondrial genomes. Several model organisms or cell lines are usually employed to understand the mechanisms underlying diseases, yeast being one of them. However, in the case of mutations within the mitochondrial genome, yeast is a major model because it is a facultative aerobe and its mitochondrial genome can be genetically engineered and reintroduced in vivo. In this short review, I will describe how these properties can be exploited to mimic mitochondrial pathogenic mutations, as well as their limits. In particular; pathological mutations of tRNA, cytb, and ATPase genes have been successfully modeled. It is essential to stress that what has been discovered with yeast (molecular mechanisms underlying the diseases, nuclear correcting genes, import of tRNA into mitochondria or compounds from drug screening has been successfully transferred to human patient lines, paving the way for future therapies.

  15. The influence of age and aerobic fitness

    DEFF Research Database (Denmark)

    Hey-Mogensen, M; Rabøl, R; Stride, N;

    2012-01-01

    Mitochondrial function has previously been studied in ageing, but never in humans matched for maximal oxygen uptake ((V)·O2max). Furthermore, the influence of ageing on mitochondrial substrate sensitivity is not known....

  16. Scoliosis in Mitochondrial Myopathy

    OpenAIRE

    Li, Zheng; Shen, Jianxiong; Liang, Jinqian

    2015-01-01

    Abstract The mitochondrial myopathies include a diverse group of disorders characterized by morphological abnormalities of muscle mitochondria. Little is reported about spinal deformity associated with this syndrome. This study presents a case of scoliosis occurring in the setting of mitochondrial myopathies and explores the possible mechanisms between the 2 diseases. A previously unreported scoliosis in mitochondrial myopathies is described. The patient was a 16-year-old Chinese adolescent b...

  17. Altered Mitochondrial Dynamics and TBI Pathophysiology.

    Science.gov (United States)

    Fischer, Tara D; Hylin, Michael J; Zhao, Jing; Moore, Anthony N; Waxham, M Neal; Dash, Pramod K

    2016-01-01

    Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS), and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI) reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1), which translocates to the mitochondrial outer membrane (MOM) to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 h post-injury, followed by a significant decrease in length at 72 h. Post-TBI administration of Mitochondrial division inhibitor-1 (Mdivi-1), a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the

  18. Evaluation of the H+/site ratio of mitochondrial electron transport from rate measurements.

    Science.gov (United States)

    Reynafarje, B; Brand, M D; Lehninger, A L

    1976-12-10

    The mitochondrial H+/site ratio (i.e. the number of protons ejected per pair of electrons traversing each of the energy-conserving sites of the respiratory chain) has been evaluated employing a new experimental approach. In this method the rates of oxygen uptake and H+ ejection were measured simultaneously during the initial period of respiration evoked by addition of succinate to aerobic, rotenone-inhibited, de-energized mitochondria. Either K+, in the presence of valinomycin, or Ca2+, was used as mobile cation to dissipate the membrane potential and allow quantitative H+ ejection into the medium. The H+/site ratio observed with this method in the absence of precautions to inhibit the uptake of phosphate was close to 2.0, in agreement with values obtained using the oxygen pulse technique (Mitchell, P. and Moyle, J. (1967) Biochem. J. 105, 1147-1162). However, when phosphate movements were eliminated either by inhibition of the phosphate-hydroxide antiporter with N-ethylamaleimide or by depleting the mitochondria of their endogenous phosphate content, H+/site ratios close to 4.0 were consistently observed. This ratio was independent of the concentration of succinate, of mitochondrial protein, of pH between 6 and 8, and of ionic composition of the medium, provided that sufficient K+ (plus valinomycin) or Ca2+ were present. Specific inhibitors of the hydrolysis of endogenous ATP or transport of other ions (adenine nucleotides, tricarboxylates, HCO3-, etc.) were shown not to affect the observed H+/site ratio. Furthermore, the replacement of succinate by alpha-glycerol phosphate, a substrate which is oxidized on the outer surface of the inner membrane and thus does not need to enter the matrix, gave the same H+/site ratios as did succinate. It is concluded that the H+/site ratio of mitochondrial electron transport, when phosphate movements are eliminated, may be close to 4.0.

  19. Evaluation of the H+/site ratio of mitochondrial electron transport from rate measurements.

    Science.gov (United States)

    Reynafarje, B; Brand, M D; Lehninger, A L

    1976-12-10

    The mitochondrial H+/site ratio (i.e. the number of protons ejected per pair of electrons traversing each of the energy-conserving sites of the respiratory chain) has been evaluated employing a new experimental approach. In this method the rates of oxygen uptake and H+ ejection were measured simultaneously during the initial period of respiration evoked by addition of succinate to aerobic, rotenone-inhibited, de-energized mitochondria. Either K+, in the presence of valinomycin, or Ca2+, was used as mobile cation to dissipate the membrane potential and allow quantitative H+ ejection into the medium. The H+/site ratio observed with this method in the absence of precautions to inhibit the uptake of phosphate was close to 2.0, in agreement with values obtained using the oxygen pulse technique (Mitchell, P. and Moyle, J. (1967) Biochem. J. 105, 1147-1162). However, when phosphate movements were eliminated either by inhibition of the phosphate-hydroxide antiporter with N-ethylamaleimide or by depleting the mitochondria of their endogenous phosphate content, H+/site ratios close to 4.0 were consistently observed. This ratio was independent of the concentration of succinate, of mitochondrial protein, of pH between 6 and 8, and of ionic composition of the medium, provided that sufficient K+ (plus valinomycin) or Ca2+ were present. Specific inhibitors of the hydrolysis of endogenous ATP or transport of other ions (adenine nucleotides, tricarboxylates, HCO3-, etc.) were shown not to affect the observed H+/site ratio. Furthermore, the replacement of succinate by alpha-glycerol phosphate, a substrate which is oxidized on the outer surface of the inner membrane and thus does not need to enter the matrix, gave the same H+/site ratios as did succinate. It is concluded that the H+/site ratio of mitochondrial electron transport, when phosphate movements are eliminated, may be close to 4.0. PMID:12164

  20. Aerobic Development of Elite Youth Ice Hockey Players.

    Science.gov (United States)

    Leiter, Jeff R; Cordingley, Dean M; MacDonald, Peter B

    2015-11-01

    Ice hockey is a physiologically complex sport requiring aerobic and anaerobic energy metabolism. College and professional teams often test aerobic fitness; however, there is a paucity of information regarding aerobic fitness of elite youth players. Without this knowledge, training of youth athletes to meet the standards of older age groups and higher levels of hockey may be random, inefficient, and or effective. Therefore, the purpose of this study was to determine the aerobic fitness of elite youth hockey players. A retrospective database review was performed for 200 male AAA hockey players between the ages of 13 and 17 (age, 14.4 ± 1.2 years; height, 174.3 ± 8.5 cm; body mass, 67.2 ± 11.5 kg; body fat, 9.8 ± 3.5%) before the 2012-13 season. All subjects performed a graded exercise test on a cycle ergometer, whereas expired air was collected by either a Parvo Medics TrueOne 2400 or a CareFusion Oxycon Mobile metabolic cart to determine maximal oxygen consumption (V[Combining Dot Above]O2max). Body mass, absolute V[Combining Dot Above]O2max, and the power output achieved during the last completed stage increased in successive age groups from age 13 to 15 years (p ≤ 0.05). Ventilatory threshold (VT) expressed as a percentage of V[Combining Dot Above]O2max and the heart rate (HR) at which VT occurred decreased between the ages of 13 and 14 years (p ≤ 0.05), whereas the V[Combining Dot Above]O2 at which VT occurred increased from the age of 14-15 years. There were no changes in relative V[Combining Dot Above]O2max or HRmax between any successive age groups. The aerobic fitness levels of elite youth ice hockey players increased as players age and mature physically and physiologically. However, aerobic fitness increased to a lesser extent at older ages. This information has the potential to influence off-season training and maximize the aerobic fitness of elite amateur hockey players, so that these players can meet standards set by advanced elite age groups.

  1. Uncoupling Mitochondrial Respiration for Diabesity.

    Science.gov (United States)

    Larrick, James W; Larrick, Jasmine W; Mendelsohn, Andrew R

    2016-08-01

    Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity. PMID:27378359

  2. Mitochondrial morphology and cardiovascular disease

    OpenAIRE

    Ong, Sang-Bing; Hausenloy, Derek J

    2010-01-01

    Mitochondria are dynamic and are able to interchange their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins (mitofusins 1 and 2, and optic atrophy 1) and the mitochondrial fission proteins (dynamin-related peptide 1 and mitochondrial fission protein 1) and have been implicated in a...

  3. Aerobic rice mechanization: techniques for crop establishment

    Science.gov (United States)

    Khusairy, K. M.; Ayob, H.; Chan, C. S.; Fauzi, M. I. Mohamed; Mohamad Fakhrul, Z. O.; Shahril Shah, G. S. M.; Azlan, O.; Rasad, M. A.; Hashim, A. M.; Arshad, Z.; E, E. Ibrahim; Saifulizan, M. N.

    2015-12-01

    Rice being the staple food crops, hundreds of land races in it makes the diversity of rice crops. Aerobic rice production was introduced which requires much less water input to safeguard and sustain the rice production and conserve water due to decreasing water resources, climatic changes and competition from urban and industrial users. Mechanization system plays an important role for the success of aerobic rice cultivation. All farming activities for aerobic rice production are run on aerobic soil conditions. Row seeder mechanization system is developed to replace conventional seeding technique on the aerobic rice field. It is targeted for small and the large scale aerobic rice farmers. The aero - seeder machine is used for the small scale aerobic rice field, while the accord - seeder is used for the large scale aerobic rice field. The use of this mechanization machine can eliminate the tedious and inaccurate seeding operations reduce labour costs and increases work rate. The machine is easy to operate and it can increase crop establishment rate. It reduce missing hill, increasing planting and crop with high yield can be produce. This machine is designed for low costs maintenance and it is easy to dismantle and assemble during maintenance and it is safe to be used.

  4. Skeletal Muscle Hypertrophy after Aerobic Exercise Training

    OpenAIRE

    Konopka, Adam R.; Harber, Matthew P.

    2014-01-01

    Current dogma suggests aerobic exercise training has minimal effect on skeletal muscle size. We and others have demonstrated that aerobic exercise acutely and chronically alters protein metabolism and induces skeletal muscle hypertrophy. These findings promote an antithesis to the status quo by providing novel perspective on skeletal muscle mass regulation and insight into exercise-countermeasures for populations prone to muscle loss.

  5. May “Mitochondrial Eve” and Mitochondrial Haplogroups Play a Role in Neurodegeneration and Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Elena Caldarazzo Ienco

    2011-01-01

    Full Text Available Mitochondria, the powerhouse of the cell, play a critical role in several metabolic processes and apoptotic pathways. Multiple evidences suggest that mitochondria may be crucial in ageing-related neurodegenerative diseases. Moreover, mitochondrial haplogroups have been linked to multiple area of medicine, from normal ageing to diseases, including neurodegeneration. Polymorphisms within the mitochondrial genome might lead to impaired energy generation and to increased amount of reactive oxygen species, having either susceptibility or protective role in several diseases. Here, we highlight the role of the mitochondrial haplogroups in the pathogenetic cascade leading to diseases, with special attention to Alzheimer's disease.

  6. Estimation of free energy barriers in the cytoplasmic and mitochondrial aspartate aminotransferase reactions probed by hydrogen-exchange kinetics of C alpha-labeled amino acids with solvent

    Energy Technology Data Exchange (ETDEWEB)

    Julin, D.A.; Wiesinger, H.; Toney, M.D.; Kirsch, J.F. (Univ. of California, Berkeley (USA))

    1989-05-02

    The existence of the postulated quinonoid intermediate in the cytoplasmic aspartate amino-transferase catalyzed transamination of aspartate to oxaloacetate was probed by determining the extent of transfer of tritium from the C alpha position of tritiated L-aspartate to pyridoxamine 5'-phosphate in single turnover experiments in which washout from the back-reaction was obviated by product trapping. The maximum amount of transferred tritium observed was 0.7%, consistent either with a mechanism in which a fraction of the net transamination reaction proceeds through a quinonoid intermediate or with a mechanism in which this intermediate is formed off the main reaction pathway. It is shown that transfer of labeled hydrogen from the amino acid to cofactor cannot be used to differentiate a stepwise from a concerted transamination mechanism. The amount of tritium transferred is a function of the rate constant for torsional equilibration about the epsilon-amino group of Lys-258, the presumptive abstractor of the C alpha proton; the relative rate constants for hydrogen exchange with solvent versus cofactor protonation; and the tritium isotope effect on this ratio. The free energy barriers facing the covalent intermediate between aldimine and keto acid product (i.e., ketimine and possibly quinonoid) were evaluated relatively by comparing the rates of C alpha-hydrogen exchange in starting amino acid with the rates of keto acid formation. The value of theta (= kexge/kprod) was found to be 2.6 for the reaction of cytoplasmic isozyme with aspartate and ca. 0.5 for that of the mitochondrial form with glutamate.

  7. Alterations in energy/redox metabolism induced by mitochondrial and environmental toxins: a specific role for glucose-6-phosphate-dehydrogenase and the pentose phosphate pathway in paraquat toxicity.

    Science.gov (United States)

    Lei, Shulei; Zavala-Flores, Laura; Garcia-Garcia, Aracely; Nandakumar, Renu; Huang, Yuting; Madayiputhiya, Nandakumar; Stanton, Robert C; Dodds, Eric D; Powers, Robert; Franco, Rodrigo

    2014-09-19

    Parkinson's disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat "hijacks" the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations in

  8. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation

    Science.gov (United States)

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-01-01

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size. DOI: http://dx.doi.org/10.7554/eLife.13374.001 PMID:27282387

  9. Ischemia/reperfusion impairs mitochondrial energy conservation and triggers O2.- release as a byproduct of respiration.

    Science.gov (United States)

    Nohl, H; Koltover, V; Stolze, K

    1993-01-01

    The aim of the present study was to elucidate the role of mitochondria in the development of heart failure following ischemia/reperfusion. Although mitochondria were increasingly assumed to be responsible for the establishment of an oxidative stress situation the lack of suitable methods to prove it required new concepts for an evaluation of the validity of this hypothesis. The principal idea was to expose isolated mitochondria to metabolic conditions which are developed during ischemia/reperfusion in the cell (anoxia, lactogenesis) and study how they respond. Heart mitochondria treated in that way responded with an incomplete collapse of the transmembraneous proton gradient, thereby impairing respiration-linked ATP generation. The membrane effect affected also the proper control of e- transfer through redox-cycling ubisemiquinone. Electrons were found to leak at this site from its normal pathway to O2 suggesting that ubisemiquinone becomes an active O2.- generator. It was concluded from these observations that mitochondria are likely to play a pathogenetic role in the reperfusion injury of the heart both, by an impairment of energy conservation and their transition to a potent O2.(-)-radical generator. Furthermore, there is considerable evidence that the exogenous NADH-dehydrogenase of heart mitochondria is mainly responsible for functional changes of these organelles during ischemia/reperfusion. PMID:8319923

  10. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.

  11. Mitochondrial DNA response to high altitude: a new perspective on high-altitude adaptation.

    Science.gov (United States)

    Luo, Yongjun; Yang, Xiaohong; Gao, Yuqi

    2013-08-01

    Mitochondria are the energy metabolism centers of the cell. More than 95% of cellular energy is produced by mitochondrial oxidative phosphorylation. Hypoxia affects a wide range of energy generation and consumption processes in animals. The most important mechanisms limiting ATP consumption increase the efficiency of ATP production and accommodate the reduced production of ATP by the body. All of these mechanisms relate to changes in mitochondrial function. Mitochondrial function can be affected by variations in mitochondrial DNA, including polymorphisms, content changes, and deletions. These variations play an important role in acclimatization or adaptation to hypoxia. In this paper, the association between mitochondrial genome sequences and high-altitude adaptation is reviewed.

  12. mtDNA D-loop多态性与澳大利亚自行车运动员有氧运动能力关系初探%A PRELIMINARY INVESTIGATION ON THE ASSOCIATION BETWEEN THE RESTRICTION FRAGMENT LENGTH POLYMORPHISMS OF THE MITOCHONDRIAL DNA DISPLACEMENT LOOP AND AEROBIC PERFORMANCE IN AUSTRALIAN ENDURANCE CYCLISTS

    Institute of Scientific and Technical Information of China (English)

    Matthew; Brearley

    2001-01-01

    This investigation was to test the hypothesis that the mitochondrial DNA displacement loop polymorphisms (morphs) are related to the differences in maximum oxygen consumption (VO2max) and endurance performance of Australian endurance cyclists. The preliminary findings demonstrate no difference in frequency of morphs between elite and non-elite cyclists, in spite of significant differences in VO2max.%研究目的:探讨了mtDNA D-loop多态性与澳大利亚自行车运动员的VO2max及优异耐力成绩的关系.研究结果:前期研究发现虽然运动员组和对照组VO2max有显著性差异,但mtDNA D-loop的多态性在两组的分布频率没有显著性差异.

  13. Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

    Directory of Open Access Journals (Sweden)

    Antonio eZorzano

    2015-06-01

    Full Text Available Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1 cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction.

  14. Computationally driven, quantitative experiments discover genes required for mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    David C Hess

    2009-03-01

    Full Text Available Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an increase of about 25% over previously known participants. Nearly half of these newly characterized proteins are conserved in mammals, including several orthologs known to be involved in human disease. Mutations in many of these genes demonstrate statistically significant mitochondrial transmission phenotypes more subtle than could be detected by traditional genetic screens or high-throughput techniques, and 47 have not been previously localized to mitochondria. We further characterized a subset of these genes using growth profiling and dual immunofluorescence, which identified genes specifically required for aerobic respiration and an uncharacterized cytoplasmic protein required for normal mitochondrial motility. Our results demonstrate that by leveraging computational analysis to direct quantitative experimental assays, we have characterized mutants with subtle mitochondrial defects whose phenotypes were undetected by high-throughput methods.

  15. Regulation and quantification of cellular mitochondrial morphology and content

    NARCIS (Netherlands)

    Tronstad, K.J.; Nooteboom, M.; Nilsson, L.I.; Nikolaisen, J.; Sokolewicz, M.; Grefte, S.; Pettersen, I.K.; Dyrstad, S.; Hoel, F.; Willems, P.H.G.M.; Koopman, W.J.H.

    2014-01-01

    Mitochondria play a key role in signal transduction, redox homeostasis and cell survival, which extends far beyond their classical functioning in ATP production and energy metabolism. In living cells, mitochondrial content ("mitochondrial mass") depends on the cell-controlled balance between mitocho

  16. Betaine is a positive regulator of mitochondrial respiration

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Icksoo, E-mail: icksoolee@dankook.ac.kr

    2015-01-09

    Highlights: • Betaine enhances cytochrome c oxidase activity and mitochondrial respiration. • Betaine increases mitochondrial membrane potential and cellular energy levels. • Betaine’s anti-tumorigenic effect might be due to a reversal of the Warburg effect. - Abstract: Betaine protects cells from environmental stress and serves as a methyl donor in several biochemical pathways. It reduces cardiovascular disease risk and protects liver cells from alcoholic liver damage and nonalcoholic steatohepatitis. Its pretreatment can rescue cells exposed to toxins such as rotenone, chloroform, and LiCl. Furthermore, it has been suggested that betaine can suppress cancer cell growth in vivo and in vitro. Mitochondrial electron transport chain (ETC) complexes generate the mitochondrial membrane potential, which is essential to produce cellular energy, ATP. Reduced mitochondrial respiration and energy status have been found in many human pathological conditions including aging, cancer, and neurodegenerative disease. In this study we investigated whether betaine directly targets mitochondria. We show that betaine treatment leads to an upregulation of mitochondrial respiration and cytochrome c oxidase activity in H2.35 cells, the proposed rate limiting enzyme of ETC in vivo. Following treatment, the mitochondrial membrane potential was increased and cellular energy levels were elevated. We propose that the anti-proliferative effects of betaine on cancer cells might be due to enhanced mitochondrial function contributing to a reversal of the Warburg effect.

  17. Altered Mitochondrial Dynamics and TBI Pathophysiology

    Directory of Open Access Journals (Sweden)

    Tara Diane Fischer

    2016-03-01

    Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved

  18. Differences in the aerobic capacity of flight muscles between butterfly populations and species with dissimilar flight abilities.

    Directory of Open Access Journals (Sweden)

    Virve Rauhamäki

    Full Text Available Habitat loss and climate change are rapidly converting natural habitats and thereby increasing the significance of dispersal capacity for vulnerable species. Flight is necessary for dispersal in many insects, and differences in dispersal capacity may reflect dissimilarities in flight muscle aerobic capacity. In a large metapopulation of the Glanville fritillary butterfly in the Åland Islands in Finland, adults disperse frequently between small local populations. Individuals found in newly established populations have higher flight metabolic rates and field-measured dispersal distances than butterflies in old populations. To assess possible differences in flight muscle aerobic capacity among Glanville fritillary populations, enzyme activities and tissue concentrations of the mitochondrial protein Cytochrome-c Oxidase (CytOx were measured and compared with four other species of Nymphalid butterflies. Flight muscle structure and mitochondrial density were also examined in the Glanville fritillary and a long-distance migrant, the red admiral. Glanville fritillaries from new populations had significantly higher aerobic capacities than individuals from old populations. Comparing the different species, strong-flying butterfly species had higher flight muscle CytOx content and enzymatic activity than short-distance fliers, and mitochondria were larger and more numerous in the flight muscle of the red admiral than the Glanville fritillary. These results suggest that superior dispersal capacity of butterflies in new populations of the Glanville fritillary is due in part to greater aerobic capacity, though this species has a low aerobic capacity in general when compared with known strong fliers. Low aerobic capacity may limit dispersal ability of the Glanville fritillary.

  19. Modulation of the matrix redox signaling by mitochondrial Ca2+

    Institute of Scientific and Technical Information of China (English)

    Jaime; Santo-Domingo; Andreas; Wiederkehr; Umberto; De; Marchi

    2015-01-01

    Mitochondria sense,shape and integrate signals,and thus function as central players in cellular signal transduction. Ca2+ waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca2+ transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance,the molecular nature of the proteins involvedin mitochondrial Ca2+ transport has been revealed only recently. Mitochondrial Ca2+ promotes energy metabolism through the activation of matrix dehydrogenases and downstream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)+ ratio,but at the same time will increase reactive oxygen species(ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state,which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redoxsensitive sensors,real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca2+ combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca2+ and redox signals and their impact on cell function. In this review,we describe mitochondrial Ca2+ handling,focusing on a number of newly identified proteins involved in mitochondrial Ca2+ uptake and release. We further discuss our recent findings,revealing how mitochondrial Ca2+ influences the matrix redox state. As a result,mitochondrial Ca2+ is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease.

  20. Inlfuence of Marine Aerobic Bioiflms on Corrosion of 316L Stainless Steel

    Institute of Scientific and Technical Information of China (English)

    Feng-ling XU; Ji-zhou DUAN; Cun-guo LIN; Bao-rong HOU

    2015-01-01

    The inlfuence of marine aerobic bioiflms on the corrosion of 316L stainless steel (SS) in aerated and deaerated seawater was studied by electrochemical impedance spectroscopy (EIS), potentiodynamic polarisation curves, current-potential curves and scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS). EIS and SEM-EDS results showed that the aero-bic bioiflms inhibited 316L SS corrosion within the test duration. Comparison of results under aerated and deaerated conditions revealed that O2 enhanced the inhibition efifciency of the aerobic bioiflms. This result indicated that living cells were necessary for the aerobic bioiflms to inhibit the corrosion of 316L SS. Polarization curves indicated that the bioiflms mainly inhibited anode ac-tion. Current-potential curves under deaerated conditions showed that electron transfer processes occurred between microorganisms and electrodes. Moreover, 316L SS as an electron acceptor was protected from corrosion.

  1. Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion.

    Science.gov (United States)

    Chen Scarabelli, Carol; McCauley, Roy B; Yuan, Zhaokan; Di Rezze, Justin; Patel, David; Putt, Jeff; Raddino, Riccardo; Allebban, Zuhair; Abboud, John; Scarabelli, Gabriele M; Chilukuri, Karuna; Gardin, Julius; Saravolatz, Louis; Faggian, Giuseppe; Mazzucco, Alessandro; Scarabelli, Tiziano M

    2008-06-01

    Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing functional performance and accelerating high-energy phosphate recovery after exhaustive exertion.

  2. Overview of mitochondrial bioenergetics.

    Science.gov (United States)

    Madeira, Vitor M C

    2012-01-01

    Bioenergetic Science started in seventh century with the pioneer works by Joseph Priestley and Antoine Lavoisier on photosynthesis and respiration, respectively. New developments were implemented by Pasteur in 1860s with the description of fermentations associated to microorganisms, further documented by Buchner brothers who discovered that fermentations also occurred in cell extracts in the absence of living cells. In the beginning of twentieth century, Harden and Young demonstrated that orthophosphate and other heat-resistant compounds (cozymase), later identified as NAD, ADP, and metal ions, were mandatory in the fermentation of glucose. The full glycolysis pathway has been detailed in 1940s with the contributions of Embden, Meyeroff, Parnas, Warburg, among others. Studies on the citric acid cycle started in 1910 (Thunberg) and were elucidated by Krebs et al. in the 1940s. Mitochondrial bioenergetics gained emphasis in the late 1940s and 1950s with the works of Lenhinger, Racker, Chance, Boyer, Ernster, and Slater, among others. The prevalent "chemical coupling hypothesis" of energy conservation in oxidative phosphorylation was challenged and replaced by the "chemiosmotic hypothesis" originally formulated in 1960s by Mitchell and later substantiated and extended to energy conservation in bacteria and chloroplasts, besides mitochondria, with clear-cut identification of molecular proton pumps. After identification of most reactive mechanisms, emphasis has been directed to structure resolution of molecular complex clusters, e.g., cytochrome c oxidase, complex III, complex II, ATP synthase, photosystem I, photosynthetic water splitting center, and energy collecting antennæ of several photosynthetic systems. Modern trends concern to the reactivity of radical and other active species in association with bioenergetic activities. A promising trend concentrates on the cell redox status quantified in terms of redox potentials. In spite of significant development and

  3. Low aerobic fitness in Brazilian adolescents

    Directory of Open Access Journals (Sweden)

    Diego Augusto Santos Silva

    2015-04-01

    Full Text Available INTRODUCTION: aerobic fitness is considered one of the most important components of health-related physical fitness, with low levels related to increased risk of premature death from all causes, especially cardiovascular diseases. OBJECTIVE: to identify the characteristics of adolescents at higher risk of low levels of aerobic fitness. METHODS: the study included 696 adolescents 15-17 years of age enrolled in public high schools of Florianópolis, southern Brazil. This cross-sectional epidemiological study was conducted in Florianópolis, Santa Catarina, Brazil. Aerobic fitness was measured using the modified Canadian Aerobic Fitness Test mCAFT. Sociodemographic gender, age, school grade, paternal and maternal schooling, socioeconomic status, and anthropometric variables body weight, height, triceps and subscapular skinfold thickness, sexual maturation, physical activity, sedentary behavior, and eating habits were collected. RESULTS: it was found that 31.5% of adolescents had low aerobic fitness levels, being higher in boys 49.2% compared to girls 20.6%. Moreover, girls with sedentary behavior, overweight and high body fat percentage were the groups most likely to have inadequate aerobic fitness. In males, the groups most likely to have inadequate aerobic fitness were those whose parents studied more than eight years, those with low levels of physical activity, and those with inadequate nutrition and excessive body fat. CONCLUSION: low aerobic fitness levels were present in one third of adolescents and was more prevalent in boys. Lifestyle changes, including replacement of sedentary behaviors by physical and sport activities , may assist in improving the aerobic fitness of Brazilian adolescents.

  4. Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis

    NARCIS (Netherlands)

    ter Veld, F; Jeneson, JAL; Nicolay, K

    2005-01-01

    Adaptations of the kinetic properties of mitochondria in striated muscle lacking cytosolic (M) and/or mitochondrial (Mi) creatine kinase (CK) isoforms in comparison to wild-type (WT) were investigated in vitro. Intact mitochondria were isolated from heart and gastrocnemius muscle of WT and single- a

  5. Mitochondrial transcription termination factor 2 binds to entire mitochondrial DNA and negatively regulates mitochondrial gene expression

    Institute of Scientific and Technical Information of China (English)

    Weiwei Huang; Min Yu; Yang Jiao; Jie Ma; Mingxing Ma; Zehua Wang; Hong Wu; Deyong Tan

    2011-01-01

    Mitochondrial transcription termination factor 2 (mTERF2) is a mitochondriai matrix protein that binds to the mitochondriai DNA.Previous studies have shown that overexpression of mTERF2 can inhibit cell proliferation, but the mechanism has not been well defined so far.This study aimed to present the binding pattern of mTERF2 to the mitochondrial DNA (mtDNA) in vivo, and investigated the biological function of mTERF2 on the replication of mtDNA, mRNA transcription, and protein translation.The mTERF2 binding to entire mtDNA was identified via the chromatin immunoprecipitation analysis.The mtDNA replication efficiency and expression levels of mitochondria genes were significantly inhibited when the mTERF2 was overexpressed in HeLa cells.The inhibition level of mtDNA content was the same with the decreased levels of mRNA and mitochondrial protein expression.Overall, the mTERF2 might be a cell growth inhibitor based on its negative effect on mtDNA replication, which eventually own-regulated all of the oxidative phosphorylation components in the mitochondria that were essential for the cell's energy metabolism.

  6. Control mechanisms in mitochondrial oxidative phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Jana Hroudová; Zdeněk Fi(s)ar

    2013-01-01

    Distribution and activity of mitochondria are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5'- triphosphate production is regulated by many control mechanism–firstly by oxygen, substrate level, adenosine-5'-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by "second control mechanisms," such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, allosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5'-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria, similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.

  7. How "healthful" are aerobics classes? Exploring the health and wellness messages in aerobics classes for women.

    Science.gov (United States)

    D'Abundo, Michelle Lee

    2007-01-01

    The purpose of this study was to explore the health messages communicated by aerobics instructors in aerobics classes for women. A theoretical framework influenced by adult learning theory and feminist pedagogy was used in this qualitative study. Over a 3-month period, the practices of five aerobics instructors working at one nonprofit fitness center and one wellness facility were explored. The methods of data collection were one interview with each aerobics instructor and 14 site visits to conduct participant observations and to retrieve of documents. Despite the nonprofit and wellness-based environment of the exercise facilities in this research, there was still an overemphasis on the physical aspect of aerobics classes. Therefore, the potential wellness-related benefits of aerobics classes for women, especially in environments that identified themselves as promoting wellness, were not fully realized. PMID:17148107

  8. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment.

    Science.gov (United States)

    Niyazov, Dmitriy M; Kahler, Stephan G; Frye, Richard E

    2016-07-01

    Mitochondrial disease refers to a heterogeneous group of disorders resulting in defective cellular energy production due to abnormal oxidative phosphorylation (oxphos). Primary mitochondrial disease (PMD) is diagnosed clinically and ideally, but not always, confirmed by a known or indisputably pathogenic mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) mutation. The PMD genes either encode oxphos proteins directly or they affect oxphos function by impacting production of the complex machinery needed to run the oxphos process. However, many disorders have the 'mitochondrial' phenotype without an identifiable mtDNA or nDNA mutation or they have a variant of unknown clinical significance. Secondary mitochondrial dysfunction (SMD) can be caused by genes encoding neither function nor production of the oxphos proteins and accompanies many hereditary non-mitochondrial diseases. SMD may also be due to nongenetic causes such as environmental factors. In our practice, we see many patients with clinical signs of mitochondrial dysfunction based on phenotype, biomarkers, imaging, muscle biopsy, or negative/equivocal mtDNA or nDNA test results. In these cases, it is often tempting to assign a patient's phenotype to 'mitochondrial disease', but SMD is often challenging to distinguish from PMD. Fortunately, rapid advances in molecular testing, made possible by next generation sequencing, have been effective at least in some cases in establishing accurate diagnoses to distinguish between PMD and SMD. This is important, since their treatments and prognoses can be quite different. However, even in the absence of the ability to distinguish between PMD and SMD, treating SMD with standard treatments for PMD can be effective. We review the latest findings regarding mitochondrial disease/dysfunction and give representative examples in which differentiation between PMD and SMD has been crucial for diagnosis and treatment. PMID:27587988

  9. Formoterol Restores Mitochondrial and Renal Function after Ischemia-Reperfusion Injury

    OpenAIRE

    Jesinkey, Sean R.; Funk, Jason A.; Stallons, L. Jay; Wills, Lauren P.; Megyesi, Judit K.; Beeson, Craig C.; Schnellmann, Rick G.

    2014-01-01

    Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renal mitochondrial dysfunction has been implicated in the pathogenesis of AKI. We proposed that stimulation of mitochondrial biogenesis 24 hours after ischemia/reperfusion (I/R)–induced AKI, when renal dysfunction is maximal, would accelerate recovery of mitochondrial and renal function in mice. We recently showed that formoterol,...

  10. Mitochondrial Ca2+ transport and permeability transition pore opening and mitochondrial energetic status

    Institute of Scientific and Technical Information of China (English)

    黄行许; 翟大勇; 黄有国; 杨福愉

    2000-01-01

    The relationship between mitochondrial Ca2+ transport and permeability transition pore (PTP) opening as well as the effects of mitochondrial energetic status on mitochondrial Ca2+ transport and PTP opening were studied. The results showed that the calcium-induced calcium release from mitochondria (mClCR) induced PTP opening. Inhibitors for electron transport of respiratory chain inhibited mClCR and PTP opening. Partial recovery of electron transport in respiratory chain resulted in partial recovery of mClCR and PTP opening. mClCR and PTP opening were also inhibited by CCCP which eliminated transmembrane proton gradient. The results indicated that mitochondrial Ca2+ transport and PTP opening are largely dependent on electron transport and energy coupling.

  11. Mitochondrial Ca2+ transport and permeability transition pore opening and mitochondrial energetic status

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The relationship between mitochondrial Ca2+ transport and permeability transition pore (PTP) opening as well as the effects of mitochondrial energetic status on mitochondrial Ca2+ transport and PTP opening were studied. The results showed that the calcium-induced calcium release from mitochondria (mCICR) induced PTP opening. Inhibitors for electron transport of respiratory chain inhibited mCICR and PTP opening. Partial recovery of electron transport in respiratory chain resulted in partial recovery of mCICR and PTP opening. mCICR and PTP opening were also inhibited by CCCP which eliminated transmembrane proton gradient. The results indicated that mitochondrial Ca2+ transport and PTP opening are largely dependent on electron transport and energy coupling.

  12. United Mitochondrial Disease Foundation

    Science.gov (United States)

    ... to Mitochondrial Disease FAQ's MitoFirst Handbook More Information Mito 101 Symposium Archives Get Connected Find an Event Adult Advisory Council Team Ask The Mito Doc Grand Rounds Kids & Teens Medical Child Abuse ...

  13. Neuromodulation of Aerobic Exercise—A Review

    Directory of Open Access Journals (Sweden)

    Saskia eHeijnen

    2016-01-01

    Full Text Available Running, and aerobic exercise in general, is a physical activity that increasingly many people engage in but that also has become popular as a topic for scientific research. Here we review the available studies investigating whether and to which degree aerobic exercise modulates hormones, amino acids, and neurotransmitters levels. In general, it seems that factors such as genes, gender, training status, and hormonal status need to be taken into account to gain a better understanding of the neuromodular underpinnings of aerobic exercise. More research using longitudinal studies and considering individual differences is necessary to determine actual benefits. We suggest that, in order to succeed, aerobic exercise programs should include optimal periodization, prevent overtraining and be tailored to interindividual differences, including neuro-developmental and genetically-based factors.

  14. LHON: Mitochondrial Mutations and More.

    Science.gov (United States)

    Kirches, E

    2011-03-01

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the 'primary LHON mutations' to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs.

  15. Combined alkaline and ultrasonic pretreatment of sludge before aerobic digestion

    Institute of Scientific and Technical Information of China (English)

    JIN Yiying; LI Huan; MAHAR Rasool Bux; WANG Zhiyu; NIE Yongfeng

    2009-01-01

    Alkaline and ultrasonic sludge disintegration can both be used as pretreatments of waste activated sludge (WAS) for improving the subsequent anaerobic or aerobic digestion. The pretreatment has been carried out using different combination of these two methods in this study. The effect was evaluated based on the quantity of soluble chemical oxygen demand (SCOD) in the pretreated sludge as well as the degradation of organic matter in the following aerobic digestion. For WAS samples with combined pretreatment, the released COD was in high level than those with ultrasonic or alkaline treatment. When combined with the same ultrasonic treatment, NaOH treatment resulted in more solubilization of WAS than Ca(OH)2. For combined NaOH and ultrasonic treatments with different sequences, the released COD were in the order: simultaneous treatment > ultrasonic treatment following NaOH treatment > NaOH treatment following ultrasonic treatment. For simultaneous treatment, low NaOH dosage (100 g/kg dry solid), short duration (30 min) of NaOH treatment, and low ultrasonic specific energy (7 500 kJ/kg dry solid) were beneficial for sludge disintegration. Using combined NaOH and ultrasonic pretreatment with the optimium parameters, the degradation efficiency of organic matter was increased from 38.0% to 50.7%, which is much higher than with ultrasonic (42.5%) or with NaOH pretreatment (43.5%) in the subsequent aerobic digestion at the same retention time.

  16. Microbial fuel cells with highly active aerobic biocathodes

    Science.gov (United States)

    Milner, Edward M.; Popescu, Dorin; Curtis, Tom; Head, Ian M.; Scott, Keith; Yu, Eileen H.

    2016-08-01

    Microbial fuel cells (MFCs), which convert organic waste to electricity, could be used to make the wastewater infrastructure more energy efficient and sustainable. However, platinum and other non-platinum chemical catalysts used for the oxygen reduction reaction (ORR) at the cathode of MFCs are unsustainable due to their high cost and long-term degradation. Aerobic biocathodes, which use microorganisms as the biocatalysts for cathode ORR, are a good alternative to chemical catalysts. In the current work, high-performing aerobic biocathodes with an onset potential for the ORR of +0.4 V vs. Ag/AgCl were enriched from activated sludge in electrochemical half-cells poised at -0.1 and + 0.2 V vs. Ag/AgCl. Gammaproteobacteria, distantly related to any known cultivated gammaproteobacterial lineage, were identified as dominant in these working electrode biofilms (23.3-44.3% of reads in 16S rRNA gene Ion Torrent libraries), and were in very low abundance in non-polarised control working electrode biofilms (0.5-0.7%). These Gammaproteobacteria were therefore most likely responsible for the high activity of biologically catalysed ORR. In MFC tests, a high-performing aerobic biocathode increased peak power 9-fold from 7 to 62 μW cm-2 in comparison to an unmodified carbon cathode, which was similar to peak power with a platinum-doped cathode at 70 μW cm-2.

  17. Dosing method of physical activity in aerobics classes for students

    Directory of Open Access Journals (Sweden)

    Beliak Yu.I.

    2014-10-01

    Full Text Available Purpose : reasons for the method of dosing of physical activity in aerobics classes for students. The basis of the method is the evaluation of the metabolic cost of funds used in them. Material : experiment involved the assessment of the pulse response of students to load complexes classical and step aerobics (n = 47, age 20-23 years. In complexes used various factors regulating the intensity: perform combinations of basic steps, involvement of movements with his hands, holding in hands dumbbells weighing 1kg increase in the rate of musical accompaniment, varying heights step platform. Results . on the basis of the relationship between heart rate and oxygen consumption was determined by the energy cost of each admission control load intensity. This indicator has been used to justify the intensity and duration of multiplicity aerobics. Figure correspond to the level of physical condition and motor activity deficits students. Conclusions : the estimated component of this method of dosing load makes it convenient for use in automated computer programs. Also it can be easily modified to dispense load other types of recreational fitness.

  18. The plant mitochondrial proteome

    DEFF Research Database (Denmark)

    Millar, A.H.; Heazlewood, J.L.; Kristensen, B.K.;

    2005-01-01

    The plant mitochondrial proteome might contain as many as 2000-3000 different gene products, each of which might undergo post-translational modification. Recent studies using analytical methods, such as one-, two- and three-dimensional gel electrophoresis and one- and two-dimensional liquid...... context to be defined for them. There are indications that some of these proteins add novel activities to mitochondrial protein complexes in plants....

  19. Mitochondrial dynamics and apoptosis

    OpenAIRE

    Suen, Der-Fen; Norris, Kristi L.; Youle, Richard J.

    2008-01-01

    In healthy cells, mitochondria continually divide and fuse to form a dynamic interconnecting network. The molecular machinery that mediates this organelle fission and fusion is necessary to maintain mitochondrial integrity, perhaps by facilitating DNA or protein quality control. This network disintegrates during apoptosis at the time of cytochrome c release and prior to caspase activation, yielding more numerous and smaller mitochondria. Recent work shows that proteins involved in mitochondri...

  20. Collection of "strengthening sets" of aerobics lesson.\\\\

    OpenAIRE

    CAKL, Vojtěch

    2011-01-01

    The aim of this bachelor study was to create a strengthening sets for aerobic lessons including showing these possisions in practice on selective aerobic lessons . Based on special literature the author had chosen suitable muscle development exercises to increase the body strenth. These exercises were there practised for six weeks continuously. Before and after the research were selected individuals who were compared by 4 exact same tests to detect static and dynamic body strength. The result...

  1. Evaluation of A "Floating" Aerobics Floor

    OpenAIRE

    Favor, Craig M.

    1997-01-01

    Aerobics dance floors often produce annoying floor vibrations in adjacent parts of a building due to the rhythmic impact of the aerobicists. Various types of shock absorbing aerobics and dance floors are widely used to prevent injuries to the participants, but the floors may not prevent vibrations in adjacent areas of the building. The purpose of this investigation is to evaluate a temporary "floating" concrete a...

  2. Temperature effect on aerobic denitrification and nitrification

    Institute of Scientific and Technical Information of China (English)

    XIE Shu-guang; ZHANG Xiao-jian; WANG Zhan-sheng

    2003-01-01

    Nitrogen loss without organic removal in biofilter was observed and its possible reason was explained. A lower hydraulic loading could improve aerobic denitrification rate. Aerobic denitrification was seriously affected by low temperature(below 10oC). However, nitrification rate remained high when the temperature dropped from 15oC to5oC. It seemed the autotrophic biofilm in BAF could alleviate the adverse effect of low temperature.

  3. Structural organization of the mitochondrial respiratory chain.

    Science.gov (United States)

    Genova, Maria Luisa; Bianchi, Cristina; Lenaz, Giorgio

    2003-03-01

    Two models exist of the mitochondrial respiratory chain: the model of a random organization of the individual respiratory enzyme complexes and that of a super-complex assembly formed by stable association between the individual complexes. Recently Schägger, using digitonin solubilization and Blue Native PAGE produced new evidence of preferential associations, in particular a Complex I monomer with a Complex III dimer, and suggested a model of the respiratory chain (the respirasome) based on direct electron channelling between complexes. Discrimination between the two models is amenable to kinetic testing using flux control analysis. Experimental evidence obtained in beef heart SMP, according to the extension of the Metabolic Control Theory for pathways with metabolic channelling, showed that enzyme associations involving Complex I and Complex III take place in the respiratory chain while Complex IV seems to be randomly distributed, with cytochrome c behaving as a mobile component. Flux control analysis at anyone of the respiratory complexes involved in aerobic succinate oxidation indicated that Complex II and III are not functionally associated in a stable supercomplex. A critical appraisal of the solid-state model of the mitochondrial respiratory chain requires its reconciliation with previous biophysical and kinetic evidence that CoQ behaves as a homogeneous diffusible pool between all reducing enzyme and all oxidizing enzymes: the hypothesis can be advanced that both models (CoQ pool and supercomplexes) are true, by postulating that supercomplexes physiologically exist in equilibrium with isolated complexes depending on metabolic conditions of the cell.

  4. Enhanced in situ aerobic bioremediation

    Energy Technology Data Exchange (ETDEWEB)

    Sharfe, K. [CleanEARTH Solutions Ltd., Concord, ON (Canada)

    2007-07-01

    An enhanced in situ aerobic bioremediation process was described. The process used microbe supporting emulsifications to enhance bioavailability as well as to attenuate microbe competition and boost microbial production. Microbes were added prior to application and rapidly initiated bioremediation once applied to impacted areas. The microbe supporting emulsifiers were metabolically active. The study showed that exposed surface areas increased as hydrocarbon masses were divided, which in turn increased the water/substrate interface where microbial action occurred. Nutrients were used to ensure that crowding and waste accumulation were attenuated in order to ensure that the speed of growth and reproduction progressed exponentially. Water-carrying bacteria, enzymes and nutrients were adsorbed to the soil's particle surface and then diffused between particles. The sequestered hydrocarbons were then emulsified and removed in order to be bioremediated. It was concluded that biological catalysts were used to increase microbial activity and to trigger anabolic responses in microbes. Details of a biocatalyst laboratory solution analysis were also included. tabs., figs.

  5. Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung.

    Science.gov (United States)

    Bongard, Robert D; Yan, Ke; Hoffmann, Raymond G; Audi, Said H; Zhang, Xiao; Lindemer, Brian J; Townsley, Mary I; Merker, Marilyn P

    2013-12-01

    Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 μM). Compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 µmol · g(-1) dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 to 38.62 ± 3.14 µmol · 15 min(-1) perfusion · g(-1) dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H-quinone oxidoreductase 1 or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 to 0.156 ± 0.037 ml · min(-1) · cm H2O(-1) · g(-1) dry lung, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate:pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low-molecular-weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency.

  6. Influence of aeration intensity on mature aerobic granules in sequencing batch reactor.

    Science.gov (United States)

    Gao, Da-Wen; Liu, Lin; Liang, Hong

    2013-05-01

    Aeration intensity is well known as an important factor in the formation of aerobic granules. In this research, two identical lab-scale sequencing batch reactors with aeration intensity of 0.8 (R1) and 0.2 m(3)/h (R2) were operated to investigate the characteristics and kinetics of matured aerobic granules. Results showed that both aeration intensity conditions induced granulation, but they showed different effects on the characteristics of aerobic granules. Compared with the low aeration intensity (R2), the aerobic granules under the higher aeration intensity (R1) had better physical characteristics and settling ability. However, the observed biomass yield (Y obs) in R1 [0.673 kg mixed liquor volatile suspended solids (MLVSS)/kg chemical oxygen demand (COD)] was lower than R2 (0.749 kg MLVSS/kg COD). In addition, the maximum specific COD removal rates (q max) and apparent half rate constant (K) of mature aerobic granular sludge under the two aeration intensities were at a similar level. Therefore, the matured aerobic granule system does not require to be operated in a higher aeration intensity, which will reduce the energy consumption.

  7. Aerobic fitness does not modify the effect of FTO variation on body composition traits.

    Directory of Open Access Journals (Sweden)

    Antti Huuskonen

    Full Text Available PURPOSE: Poor physical fitness and obesity are risk factors for all cause morbidity and mortality. We aimed to clarify whether common genetic variants of key energy intake determinants in leptin (LEP, leptin receptor (LEPR, and fat mass and obesity-associated (FTO are associated with aerobic and neuromuscular performance, and whether aerobic fitness can alter the effect of these genotypes on body composition. METHODS: 846 healthy Finnish males of Caucasian origin were genotyped for FTO (rs8050136, LEP (rs7799039 and LEPR (rs8179183 and rs1137101 single nucleotide polymorphisms (SNPs, and studied for associations with maximal oxygen consumption, body fat percent, serum leptin levels, waist circumference and maximal force of leg extensor muscles. RESULTS: Genotype AA of the FTO SNP rs8050136 associated with higher BMI and greater waist circumference compared to the genotype CC. In general linear model, no significant interaction for FTO genotype-relative VO(2max (mL·kg(-1·min(-1 or FTO genotype-absolute VO(2max (L·min(-1 on BMI or waist circumference was found. Main effects of aerobic performance on body composition traits were significant (p<0.001. Logistic regression modelling found no significant interaction between aerobic fitness and FTO genotype. LEP SNP rs7799039, LEPR SNPs rs8179183 and rs1137101 did not associate with any of the measured variables, and no significant interactions of LEP or LEPR genotype with aerobic fitness were observed. In addition, none of the studied SNPs associated with aerobic or neuromuscular performance. CONCLUSIONS: Aerobic fitness may not modify the effect of FTO variation on body composition traits. However, relative aerobic capacity associates with lower BMI and waist circumference regardless of the FTO genotype. FTO, LEP and LEPR genotypes unlikely associate with physical performance.

  8. Current perspectives on mitochondrial inheritance in fungi

    Directory of Open Access Journals (Sweden)

    Xu J

    2015-08-01

    Full Text Available Jianping Xu,1,2 He Li2 1Department of Biology, McMaster University, Hamilton, Canada; 2The Key Laboratory for Non-Wood Forest Cultivation and Conservation of the Federal Ministry of Education, Central South University of Forestry and Technology, Changsha, People’s Republic of China Abstract: The mitochondrion is an essential organelle of eukaryotes, generating the universal energy currency, adenosine triphosphate, through oxidative phosphorylation. However, aside from generation of adenosine triphosphate, mitochondria have also been found to impact a diversity of cellular functions and organ system health in humans and other eukaryotes. Thus, inheriting and maintaining functional mitochondria are essential for cell health. Due to the relative ease of conducting genetic and molecular biological experiments using fungi, they (especially the budding yeast Saccharomyces cerevisiae have been used as model organisms for investigating the patterns of inheritance and intracellular dynamics of mitochondria and mitochondrial DNA. Indeed, the diversity of mitochondrial inheritance patterns in fungi has contributed to our broad understanding of the genetic, cellular, and molecular controls of mitochondrial inheritance and their evolutionary implications. In this review, we briefly summarize the patterns of mitochondrial inheritance in fungi, describe the genes and processes involved in controlling uniparental mitochondrial DNA inheritance in sexual crosses in basidiomycete yeasts, and provide an overview of the molecular and cellular processes governing mitochondrial inheritance during asexual budding in S. cerevisiae. Together, these studies reveal that complex regulatory networks and molecular processes are involved in ensuring the transmission of healthy mitochondria to the progeny. Keywords: uniparental inheritance, biparental inheritance, mating type, actin cable, mitochore, mitochondrial partition 

  9. Targeting Tumor Mitochondrial Metabolism Overcomes Resistance to Antiangiogenics

    Directory of Open Access Journals (Sweden)

    Paloma Navarro

    2016-06-01

    Full Text Available Epithelial malignancies are effectively treated by antiangiogenics; however, acquired resistance is a major problem in cancer therapeutics. Epithelial tumors commonly have mutations in the MAPK/Pi3K-AKT pathways, which leads to high-rate aerobic glycolysis. Here, we show how multikinase inhibitor antiangiogenics (TKIs induce hypoxia correction in spontaneous breast and lung tumor models. When this happens, the tumors downregulate glycolysis and switch to long-term reliance on mitochondrial respiration. A transcriptomic, metabolomic, and phosphoproteomic study revealed that this metabolic switch is mediated by downregulation of HIF1α and AKT and upregulation of AMPK, allowing uptake and degradation of fatty acids and ketone bodies. The switch renders mitochondrial respiration necessary for tumor survival. Agents like phenformin or ME344 induce synergistic tumor control when combined with TKIs, leading to metabolic synthetic lethality. Our study uncovers mechanistic insights in the process of tumor resistance to TKIs and may have clinical applicability.

  10. Drosophila clueless is highly expressed in larval neuroblasts, affects mitochondrial localization and suppresses mitochondrial oxidative damage.

    Directory of Open Access Journals (Sweden)

    Aditya Sen

    Full Text Available Mitochondria are critical for neuronal function due to the high demand of ATP in these cell types. During Drosophila development, neuroblasts in the larval brain divide asymmetrically to populate the adult central nervous system. While many of the proteins responsible for maintaining neuroblast cell fate and asymmetric cell divisions are known, little is know about the role of metabolism and mitochondria in neuroblast division and maintenance. The gene clueless (clu has been previously shown to be important for mitochondrial function. clu mutant adults have severely shortened lifespans and are highly uncoordinated. Part of their lack of coordination is due to defects in muscle, however, in this study we have identified high levels of Clu expression in larval neuroblasts and other regions of the dividing larval brain. We show while mitochondria in clu mutant neuroblasts are mislocalized during the cell cycle, surprisingly, overall brain morphology appears to be normal. This is explained by our observation that clu mutant larvae have normal levels of ATP and do not suffer oxidative damage, in sharp contrast to clu mutant adults. Mutations in two other genes encoding mitochondrial proteins, technical knockout and stress sensitive B, do not cause neuroblast mitochondrial mislocalization, even though technical knockout mutant larvae suffer oxidative damage. These results suggest Clu functions upstream of electron transport and oxidative phosphorylation, has a role in suppressing oxidative damage in the cell, and that lack of Clu's specific function causes mitochondria to mislocalize. These results also support the previous observation that larval development relies on aerobic glycolysis, rather than oxidative phosphorylation. Thus Clu's role in mitochondrial function is not critical during larval development, but is important for pupae and adults.

  11. Fatty Acids in Energy Metabolism of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Alexander Panov

    2014-01-01

    Full Text Available In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain’s energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

  12. Mitochondrial dysfunction and resuscitation in sepsis.

    Science.gov (United States)

    Ruggieri, Albert J; Levy, Richard J; Deutschman, Clifford S

    2010-07-01

    Sepsis is among the most common causes of death in patients in intensive care units in North America and Europe. In the United States, it accounts for upwards of 250,000 deaths each year. Investigations into the pathobiology of sepsis have most recently focused on common cellular and subcellular processes. One possibility would be a defect in the production of energy, which translates to an abnormality in the production of adenosine triphosphate and therefore in the function of mitochondria. This article presents a clear role for mitochondrial dysfunction in the pathogenesis and pathophysiology of sepsis. What is less clear is the teleology underlying this response. Prolonged mitochondrial dysfunction and impaired biogenesis clearly are detrimental. However, early inhibition of mitochondrial function may be adaptive. PMID:20643307

  13. Mitochondrial functions on oocytes and preimplantation embryos

    Institute of Scientific and Technical Information of China (English)

    Li-ya WANG; Da-hui WANG; Xiang-yang ZOU; Chen-ming XU

    2009-01-01

    Oocyte quality has long been considered as a main limiting factor for in vitro fertilization (IVF). In the past decade,extensive observations demonstrated that the mitochondrion plays a vital role in the oocyte cytoplasm, for it can provide adenosine triphosphate (ATP) for fertilization and preimplantation embryo development and also act as stores of intracellular calcium and proapoptotic factors. During the oocyte maturation, mitochondria are characterized by distinct changes of their distribution pattern from being homogeneous to heterogeneous, which is correlated with the cumulus apoptosis. Oocyte quality decreases with the increasing maternal age. Recent studies have shown that low quality oocytes have some age-related dysfunctions, which include the decrease in mitochondrial membrane potential, increase of mitochondrial DNA (mtDNA) damages, chromosomal aneuploidies,the incidence of apoptosis, and changes in mitochondrial gene expression. All these dysfunctions may cause a high level of developmental retardation and arrest of preimplantation embryos. It has been suggested that these mitochondrial changes may arise from excessive reactive oxygen species (ROS) that is closely associated with the oxidative energy production or calcium overload,which may trigger permeability transition pore opening and subsequent apoptosis. Therefore, mitochondria can be seen as signs for oocyte quality evaluation, and it is possible that the oocyte quality can be improved by enhancing the physical function of mitochondria. Here we reviewed recent advances in mitochondrial functions on oocytes.

  14. Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Eung Yeop [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Brain Korea 21 Project for Medical Science, Seoul (Korea); Lee, Young-Mock; Lee, Joon Soo [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Kim, Heung Dong [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Yonsei University College of Medicine, Department of Pediatrics, Seoul (Korea)

    2008-08-15

    Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

  15. Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

    International Nuclear Information System (INIS)

    Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

  16. The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy.

    Science.gov (United States)

    Vincent, Amy E; Ng, Yi Shiau; White, Kathryn; Davey, Tracey; Mannella, Carmen; Falkous, Gavin; Feeney, Catherine; Schaefer, Andrew M; McFarland, Robert; Gorman, Grainne S; Taylor, Robert W; Turnbull, Doug M; Picard, Martin

    2016-01-01

    Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease. PMID:27506553

  17. Neurological mitochondrial cytopathies.

    Directory of Open Access Journals (Sweden)

    Mehndiratta M

    2002-04-01

    Full Text Available The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years. Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes, three had MERRF (myoclonic epilepsy and ragged red fibre myopathy, three cases had KSS (Kearns-Sayre Syndrome and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%. Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF.

  18. Mitochondrial fusion and inheritance of the mitochondrial genome.

    Science.gov (United States)

    Takano, Hiroyoshi; Onoue, Kenta; Kawano, Shigeyuki

    2010-03-01

    Although maternal or uniparental inheritance of mitochondrial genomes is a general rule, biparental inheritance is sometimes observed in protists and fungi,including yeasts. In yeast, recombination occurs between the mitochondrial genomes inherited from both parents.Mitochondrial fusion observed in yeast zygotes is thought to set up a space for DNA recombination. In the last decade,a universal mitochondrial fusion mechanism has been uncovered, using yeast as a model. On the other hand, an alternative mitochondrial fusion mechanism has been identified in the true slime mold Physarum polycephalum.A specific mitochondrial plasmid, mF, has been detected as the genetic material that causes mitochondrial fusion in P. polycephalum. Without mF, fusion of the mitochondria is not observed throughout the life cycle, suggesting that Physarum has no constitutive mitochondrial fusion mechanism.Conversely, mitochondria fuse in zygotes and during sporulation with mF. The complete mF sequence suggests that one gene, ORF640, encodes a fusogen for Physarum mitochondria. Although in general, mitochondria are inherited uniparentally, biparental inheritance occurs with specific sexual crossing in P. polycephalum.An analysis of the transmission of mitochondrial genomes has shown that recombinations between two parental mitochondrial genomes require mitochondrial fusion,mediated by mF. Physarum is a unique organism for studying mitochondrial fusion. PMID:20196232

  19. Regulation of Mitochondrial Function by Voltage Dependent Anion Channels in Ethanol Metabolism and the Warburg Effect

    Science.gov (United States)

    Lemasters, John J.; Holmuhamedov, Ekhson L.; Czerny, Christoph; Zhong, Zhi; Maldonado, Eduardo N.

    2012-01-01

    Voltage dependent anion channels (VDAC) are highly conserved proteins that are responsible for permeability of the mitochondrial outer membrane to hydrophilic metabolites like ATP, ADP and respiratory substrates. Although previously assumed to remain open, VDAC closure is emerging as an important mechanism for regulation of global mitochondrial metabolism in apoptotic cells and also in cells that are not dying. During hepatic ethanol oxidation to acetaldehyde, VDAC closure suppresses exchange of mitochondrial metabolites, resulting in inhibition of ureagenesis. In vivo, VDAC closure after ethanol occurs coordinately with mitochondrial uncoupling. Since acetaldehyde passes through membranes independently of channels and transporters, VDAC closure and uncoupling together foster selective and more rapid oxidative metabolism of toxic acetaldehyde to nontoxic acetate by mitochondrial aldehyde dehydrogenase. In single reconstituted VDAC, tubulin decreases VDAC conductance, and in HepG2 hepatoma cells, free tubulin negatively modulates mitochondrial membrane potential, an effect enhanced by protein kinase A. Tubulin-dependent closure of VDAC in cancer cells contributes to suppression of mitochondrial metabolism and may underlie the Warburg phenomenon of aerobic glycolysis. PMID:22172804

  20. Adult-onset mitochondrial myopathy.

    Science.gov (United States)

    Fernandez-Sola, J.; Casademont, J.; Grau, J. M.; Graus, F.; Cardellach, F.; Pedrol, E.; Urbano-Marquez, A.

    1992-01-01

    Mitochondrial diseases are polymorphic entities which may affect many organs and systems. Skeletal muscle involvement is frequent in the context of systemic mitochondrial disease, but adult-onset pure mitochondrial myopathy appears to be rare. We report 3 patients with progressive skeletal mitochondrial myopathy starting in adult age. In all cases, the proximal myopathy was the only clinical feature. Mitochondrial pathology was confirmed by evidence of ragged-red fibres in muscle histochemistry, an abnormal mitochondrial morphology in electron microscopy and by exclusion of other underlying diseases. No deletions of mitochondrial DNA were found. We emphasize the need to look for a mitochondrial disorder in some non-specific myopathies starting in adult life. Images Figure 1 Figure 2 PMID:1589382

  1. Mitochondrial approaches to protect against cardiac ischemia and reperfusion injury

    Directory of Open Access Journals (Sweden)

    Amadou K.S. Camara

    2011-04-01

    Full Text Available The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes. Mitochondria are involved in a myriad of complex signaling cascades regulating cell death vs. survival. Importantly, mitochondrial dysfunction and the resulting oxidative and nitrosative stress are central in the pathogenesis of numerous human maladies including cardiovascular diseases, neurodegenerative diseases, diabetes, and retinal diseases, many of which are related. This review will examine the emerging understanding of the role of mitochondria in the etiology and progression of cardiovascular diseases and will explore potential therapeutic benefits of targeting the organelle in attenuating the disease process. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate or manipulate mitochondrial function, to the use of light therapy directed to the mitochondrial function, and to modification of the mitochondrial genome for potential therapeutic benefit. The approach to rationally treat mitochondrial dysfunction could lead to more effective interventions in cardiovascular diseases that to date have remained elusive. The central premise of this review is that if mitochondrial abnormalities contribute to the etiology of cardiovascular diseases (e.g. ischemic heart disease, alleviating the mitochondrial dysfunction will contribute to mitigating the severity or progression of the disease. To this end, this review will provide an overview of our current understanding of mitochondria function in cardiovascular diseases as well as the potential role for targeting mitochondria with potential drugs or other interventions that lead to protection against cell injury.

  2. Intracellular Shuttle: The Lactate Aerobic Metabolism

    Directory of Open Access Journals (Sweden)

    Rogério Santos de Oliveira Cruz

    2012-01-01

    Full Text Available Lactate is a highly dynamic metabolite that can be used as a fuel by several cells of the human body, particularly during physical exercise. Traditionally, it has been believed that the first step of lactate oxidation occurs in cytosol; however, this idea was recently challenged. A new hypothesis has been presented based on the fact that lactate-to-pyruvate conversion cannot occur in cytosol, because the LDH enzyme characteristics and cytosolic environment do not allow the reaction in this way. Instead, the Intracellular Lactate Shuttle hypothesis states that lactate first enters in mitochondria and only then is metabolized. In several tissues of the human body this idea is well accepted but is quite resistant in skeletal muscle. In this paper, we will present not only the studies which are protagonists in this discussion, but the potential mechanism by which this oxidation occurs and also a link between lactate and mitochondrial proliferation. This new perspective brings some implications and comes to change our understanding of the interaction between the energy systems, because the product of one serves as a substrate for the other.

  3. [Anaerobic-aerobic infection in acute appendicitis].

    Science.gov (United States)

    Mamchich, V I; Ulitovskiĭ, I V; Savich, E I; Znamenskiĭ, V A; Beliaeva, O A

    1998-01-01

    362 patients with acute appendicitis (AA) were examined. For microbiological diagnosis of aerobic and anaerobic nonclostridial microflora we used complex accelerated methods (including evaluation of gram-negative microorganisms in comparison with tinctorial-fermentative method of differential staining according to oxygen sensitivity of catalasopositive together with aerobic and cathalasonegative anaerobic microorganisms) as well as complete bacteriologic examination with determination of sensitivity of the above microorganism to antimicrobial remedies. High rate of aerobic-anaerobic microbial associations and substantial identity of microflora from appendicis and exudate from abdominal cavity was revealed, which evidenced the leading role of endogenous microorganisms in etiology and pathogenesis of AA and peritonitis i. e. autoinfection. In patients with destructive forms of AA, complicated by peritonitis it is recommended to use the accelerated method of examination of pathologic material as well as the complete scheme of examination with the identification of the isolated microorganisms and the correction of antibiotic treatment. PMID:9511291

  4. Drying and recovery of aerobic granules.

    Science.gov (United States)

    Hu, Jianjun; Zhang, Quanguo; Chen, Yu-You; Lee, Duu-Jong

    2016-10-01

    To dehydrate aerobic granules to bone-dry form was proposed as a promising option for long-term storage of aerobic granules. This study cultivated aerobic granules with high proteins/polysaccharide ratio and then dried these granules using seven protocols: drying at 37°C, 60°C, 4°C, under sunlight, in dark, in a flowing air stream or in concentrated acetone solutions. All dried granules experienced volume shrinkage of over 80% without major structural breakdown. After three recovery batches, although with loss of part of the volatile suspended solids, all dried granules were restored most of their original size and organic matter degradation capabilities. The strains that can survive over the drying and storage periods were also identified. Once the granules were dried, they can be stored over long period of time, with minimal impact yielded by the applied drying protocols. PMID:27392096

  5. Mechanism of Kenaf Retting Using Aerobes

    Institute of Scientific and Technical Information of China (English)

    卢士森; 陈季华; 黄秀宝

    2001-01-01

    The experimental results showed that the duration of microbial retting processing of kenaf fibers by using aerobic microbe was four times shorter than that by using anaerobic microbe. The residual gum percentage,breaking strength, breaking elongation and linear density of aerobic retted kenaf bundle fibers did not show significantly difference with that of anaerobic retted kenaf bundle fibers by ANOVA-Tukey's studentized test at a = 5% except for the softness. The bioenergetic principle and the calculation of the amount of ATP produced during the decomposition processing of kenaf gums were used to explain why the retting duration in the case of using aerobic microbes was much shorter than that of using anaerobic microbes.

  6. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Jianxin Lu; Lokendra Kumar Sharma; Yidong Bai

    2009-01-01

    Alterations in oxidative phosphorylation resulting from mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA (mtDNA) mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

  7. Assessing aerobic natural attenuation of trichloroethene at four DOE sites

    Energy Technology Data Exchange (ETDEWEB)

    Koelsch, Michael C. [North Wind, Inc., Idaho Falls, ID (United States); Starr, Robert C. [North Wind, Inc., Idaho Falls, ID (United States); Sorenson, Jr., Kent S. [CDM, Inc., Denver, CO (United States)

    2005-03-01

    A 3-year Department of Energy Environmental Science Management Program (EMSP) project is currently investigating natural attenuation of trichloroethane (TCE) in aerobic groundwater. This presentation summarizes the results of a screening process to identify TCE plumes at DOE facilities that are suitable for assessing the rate of TCE cometabolism under aerobic conditions. In order to estimate aerobic degradation rates, plumes had to meet the following criteria: TCE must be present in aerobic groundwater, a conservative co-contaminant must be present and have approximately the same source as TCE, and the groundwater velocity must be known. A total of 127 TCE plumes were considered across 24 DOE sites. The four sites retained for the assessment were: (1) Brookhaven National Laboratory, OU III; (2) Paducah Gaseous Diffusion Plant, Northwest Plume; (3) Rocky Flats Environmental Technology Site, Industrialized Area--Southwest Plume and 903 Pad South Plume; and (4) Savannah River Site, A/M Area Plume. For each of these sites, a co-contaminant derived from the same source area as TCE was used as a nonbiodegrading tracer. The tracer determined the extent to which concentration decreases in the plume can be accounted for solely by abiotic processes such as dispersion and dilution. Any concentration decreases not accounted for by these processes must be explained by some other natural attenuation mechanism. Thus, ''half-lives'' presented herein are in addition to attenuation that occurs due to hydrologic mechanisms. This ''tracer-corrected method'' has previously been used at the DOE's Idaho National Engineering and Environmental Laboratory in conjunction with other techniques to document the occurrence of intrinsic aerobic cometabolism. Application of this method to other DOE sites is the first step to determining whether this might be a significant natural attenuation mechanism on a broader scale. Application of the tracer

  8. Co(salophen)-Catalyzed Aerobic Oxidation of p-Hydroquinone: Mechanism and Implications for Aerobic Oxidation Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Anson, Colin W.; Ghosh, Soumya; Hammes-Schiffer, Sharon; Stahl, Shannon S.

    2016-03-30

    Macrocyclic metal complexes and p-benzoquinones are commonly used as co-catalytic redox mediators in aerobic oxidation reactions. In an effort to gain insight into the mechanism and energetic efficiency of these reactions, we investigated Co(salophen)-catalyzed aerobic oxidation of p-hydroquinone. Kinetic and spectroscopic data suggest that the catalyst resting-state consists of an equilibrium between a CoII(salophen) complex, a CoIII-superoxide adduct, and a hydrogen-bonded adduct between the hydroquinone and the CoIII–O2 species. The kinetic data, together with density functional theory data, suggest that the turnover-limiting step features proton-coupled electron transfer from a semi-hydroquinone species and a CoIII-hydroperoxide intermediate. Additional experimental and computational data suggest that a coordinated H2O2 intermediate oxidizes a second equivalent of hydroquinone. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center, funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences. The NSF provided partial support for the EPR instrumentation (NSF CHE-0741901).

  9. Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes

    Energy Technology Data Exchange (ETDEWEB)

    Yasuzaki, Yukari; Yamada, Yuma [Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812 (Japan); Harashima, Hideyoshi, E-mail: harasima@pharm.hokudai.ac.jp [Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812 (Japan)

    2010-06-25

    Mitochondria are the principal producers of energy in cells of higher organisms. It was recently reported that mutations and defects in mitochondrial DNA (mtDNA) are associated with various mitochondrial diseases including a variety of neurodegenerative and neuromuscular diseases. Therefore, an effective mitochondrial gene therapy and diagnosis would be expected to have great medical benefits. To achieve this, therapeutic agents need to be delivered into the innermost mitochondrial space (mitochondrial matrix), which contains the mtDNA pool. We previously reported on the development of MITO-Porter, a liposome-based carrier that introduces macromolecular cargos into mitochondria via membrane fusion. In this study, we provide a demonstration of mitochondrial matrix delivery and the visualization of mitochondrial genes (mtDNA) in living cells using the MITO-Porter. We first prepared MITO-Porter containing encapsulated propidium iodide (PI), a fluorescent dye used to stain nucleic acids to detect mtDNA. We then confirmed the emission of red-fluorescence from PI by conjugation with mtDNA, when the carriers were incubated in the presence of isolated rat liver mitochondria. Finally, intracellular observation by confocal laser scanning microscopy clearly verified that the MITO-Porter delivered PI to the mitochondrial matrix.

  10. How the nucleus and mitochondria communicate in energy production during stress: nuclear MtATP6, an early-stress responsive gene, regulates the mitochondrial F₁F₀-ATP synthase complex.

    Science.gov (United States)

    Moghadam, Ali Asghar; Ebrahimie, Eemaeil; Taghavi, Seyed Mohsen; Niazi, Ali; Babgohari, Mahbobeh Zamani; Deihimi, Tahereh; Djavaheri, Mohammad; Ramezani, Amin

    2013-07-01

    A small number of stress-responsive genes, such as those of the mitochondrial F1F0-ATP synthase complex, are encoded by both the nucleus and mitochondria. The regulatory mechanism of these joint products is mysterious. The expression of 6-kDa subunit (MtATP6), a relatively uncharacterized nucleus-encoded subunit of F0 part, was measured during salinity stress in salt-tolerant and salt-sensitive cultivated wheat genotypes, as well as in the wild wheat genotypes, Triticum and Aegilops using qRT-PCR. The MtATP6 expression was suddenly induced 3 h after NaCl treatment in all genotypes, indicating an early inducible stress-responsive behavior. Promoter analysis showed that the MtATP6 promoter includes cis-acting elements such as ABRE, MYC, MYB, GTLs, and W-boxes, suggesting a role for this gene in abscisic acid-mediated signaling, energy metabolism, and stress response. It seems that 6-kDa subunit, as an early response gene and nuclear regulatory factor, translocates to mitochondria and completes the F1F0-ATP synthase complex to enhance ATP production and maintain ion homeostasis under stress conditions. These communications between nucleus and mitochondria are required for inducing mitochondrial responses to stress pathways. Dual targeting of 6-kDa subunit may comprise as a mean of inter-organelle communication and save energy for the cell. Interestingly, MtATP6 showed higher and longer expression in the salt-tolerant wheat and the wild genotypes compared to the salt-sensitive genotype. Apparently, salt-sensitive genotypes have lower ATP production efficiency and weaker energy management than wild genotypes; a stress tolerance mechanism that has not been transferred to cultivated genotypes.

  11. Measurement of mitochondrial NADH and FAD autofluorescence in live cells.

    Science.gov (United States)

    Bartolomé, Fernando; Abramov, Andrey Y

    2015-01-01

    In the process of energy production, mitochondrial networks are key elements to allow metabolism of substrates into ATP. Many pathological conditions have been associated with mitochondrial dysfunction as mitochondria are associated with a wide range of cellular processes. Therefore, any disruption in the energy production induces devastating effects that can ultimately lead to cell death due to chemical ischemia. To address the mitochondrial health and function, there are several bioenergetic parameters reflecting either whole mitochondrial functionality or individual mitochondrial complexes. Particularly, metabolism of nutrients in the tricarboxylic acid cycle provides substrates used to generate electron carriers (nicotinamide adenine dinucleotide [NADH] and flavin adenine dinucleotide [FADH2]) which ultimately donate electrons to the mitochondrial electron transport chain. The levels of NADH and FADH2 can be estimated through imaging of NADH/NAD(P)H or FAD autofluorescence. This report demonstrates how to perform and analyze NADH/NAD(P)H and FAD autofluorescence in a time-course-dependent manner and provides information about NADH and FAD redox indexes both reflecting the activity of the mitochondrial electron transport chain (ETC). Furthermore, total pools of NADH and FAD can be estimated providing information about the rate of substrate supply into the ETC. Finally, the analysis of NADH autofluorescence after induction of maximal respiration can offer information about the pentose phosphate pathway activity where glucose can be alternatively oxidized instead of pyruvate. PMID:25631020

  12. Mitochondrial Dysfunction in Cancer

    Directory of Open Access Journals (Sweden)

    Michelle L Boland

    2013-12-01

    Full Text Available A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability and other more conventional aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the sigificance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis and spatial dynamics and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knockon effects for cell proliferation and growth. Scientifically, there is also scope for defining what mitochondria dysfunction is and here we address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment.

  13. Changes of the sweet taste sensitivity due to aerobic physical exercise

    Directory of Open Access Journals (Sweden)

    Ni Luh Putu Ayu Wardhani

    2011-03-01

    Full Text Available Background: Sweet taste is a pleasant sensation. Sweet taste is mostly consumed and fancied by many people. Physiologically, glucose is body's source of energy, but if over used it can be affected to the body's metabolism. This can be worsen if the person's not doing a healthy lifestyle. One way to implement a healthy lifestyle is by doing physical exercises. Purpose: The aim of this study was to determine changes in sensory sensitivity of sweet taste due to aerobic physical exercise. Methods: This study was conducted on subjects aged 20 to 30 years. The subjects did aerobic exercise using 80% load of MHR. The measurement sensitivity of the senses of the sweet taste was done for three times before the subject take aerobic physical exercise, four weeks after doing aerobic physical exercise, and eight weeks after doing aerobic physical exercise. Results: There was significant difference towards sensitivity of sweet taste sense before doing aerobic physical exercise, 4 week after doing the aerobic physical exercise, and 8 week after doing aerobic physical exercise. Conclusion: Aerobic physical exercise during eight weeks increase sweet taste sensitivity.Latar belakang: Rasa manis memberikan sensasi yang menyenangkan. Rasa manis merupakan jenis rasa yang paling banyak dikonsumsi dan disukai oleh sekelompok orang. Secara fisiologis, glukosa bisa berperan sebagai sumber energi, namun apabila dikonsumsi secara berlebihan dapat menimbulkan efek patologis. Hal ini dihubungkan dengan individu yang mempunyai gaya hidup yang tidak sehat. Salah satu cara yang bisa dilakukan untuk membiasakan gaya hidup sehat adalah dengan latihan fisik (olah raga. Tujuan: Penelitian ini bertujuan untuk membuktikan adanya perubahan sensitivitas indera kecap rasa manis setelah melakukan latihan fisik aerobik. Metode: Penelitian ini melibatkan subyek laki-laki, berusia 20–30 tahun. Subjek melakukan latihan fisik aerobik dengan intensitas sebesar 80% maximal heart rate

  14. ANAEROBIC AND AEROBIC TREATMENT OF CHLORINATED ALIPHATIC COMPOUNDS

    Science.gov (United States)

    Biological degradation of 12 chlorinated aliphatic compounds (CACs) was assessed in bench-top reactors and in serum bottle tests. Three continuously mixed daily batch-fed reactor systems were evaluated: anaerobic, aerobic, and sequential-anaerobic-aerobic (sequential). Glucose,...

  15. A randomised trial comparing weight loss with aerobic exercise in overweight individuals with coronary artery disease

    DEFF Research Database (Denmark)

    Pedersen, Lene Rørholm Engelbrecht; Olsen, Rasmus H; Jürs, Anders;

    2015-01-01

    BACKGROUND: We aimed to compare the effect of aerobic interval training (AIT) versus a low energy diet (LED) on physical fitness, body composition, cardiovascular risk factors and symptoms in overweight individuals with coronary artery disease (CAD). METHODS AND DESIGN: Seventy non...

  16. THE RATE AND NATURE OF WOMEN INJURIES IN STEP AEROBICS

    OpenAIRE

    Gholam Ali Ghasemi; Vahid Zolaktaf; Fereshteh Kazemi

    2011-01-01

    Step aerobics is a form of aerobic exercise that utilizes a 90×45×20 centimeter platform. ItsInternational competitions are held annually. This sport is popular in Iranian specialist femalesport clubs and its national competitions are growing gradually. The purpose of this survey wasto determine the rate and nature of sport injury in Iranian athletes of step aerobics. Weadministered a structured interview using a modified version of standard questionnaire of"Aerobics Pathology". The populatio...

  17. ASSOCIATION BETWEEN SARCOPENIA-RELATED PHENOTYPES AND AEROBIC CAPACITY INDEXES OF OLDER WOMEN

    Directory of Open Access Journals (Sweden)

    Lídia Mara Aguiar Bezerra

    2009-09-01

    Full Text Available The purpose of the present study was to examine the association between fat-free mass (FFM, quadriceps strength and sarcopenia with aerobic fitness indexes of elderly women. A total of 189 volunteers (66.7 ± 5.46 years underwent aerobic capacity measurement through a symptom-limited cardiopulmonary exercise test to determine their individual ventilatory thresholds (VT and peak oxygen uptake (VO2 peak. Quadriceps muscle strength was assessed using an isokinetic dynamometer. Also, dual energy X-ray absorptiometry was used to assess FFM and cutoff values were used to classify subjects as sarcopenic or nonsarcopenic. Correlations, student t-test and analysis of variance were used to examine the data. Both FFM and quadriceps strength variables were positively and significantly correlated with the measured aerobic capacity indexes. These results were observed for peak exercise as well as for ventilatory thresholds. Individuals classified as sarcopenic presented significantly lower muscle strength and (VO2 peak when compared to nonsarcopenic. It can be concluded that FFM and quadriceps strength are significantly related to aerobic capacity indexes in older women, and that besides presenting lower quadriceps strength, women classified as sarcopenic have lower peak oxygen consumption. Taken together, the present results indicate that both FFM and strength play a role in the age-related decline of aerobic capacity

  18. Effect of Supplemental Ascorbic Acid on the Aerobic Capacity in Children

    Directory of Open Access Journals (Sweden)

    Gholamreza Sharifi

    2014-10-01

    Full Text Available Introduction: ascorbic acid is a water-soluble vitamin solved in water that acts as a helper of some the enzymes in the reactions of energy metabolism. Thus, the study aims to investigate the use of supplemental ascorbic acid on the aerobic and anaerobic capacity of the children.Methodology: Participants of this quasi-experimental study were 18 children in Esfahan who were randomly selected and divided into 9 groups in pair (aerobic exercise group and the control group. For 10 days before the start of the main trial, the participants in the control group received placebo and the experimental group received ascorbic acid. The average aerobic capacity was measured before and after 10 days of the use of ascorbic acid. The results were analyzed by SPSS version 18.Results: Before and after 10 days of the use of ascorbic acid, the mean and standard deviation of the aerobic capacity of the experimental group were respectively 3.59± 0.38 and 4.23 ± 0.77 and of the control group were 3.7 ± 0.40 and 3.7± 0.53, respectively. Therefore, there was a significant relationship between the use of ascorbic acid and placebo in terms of aerobic capacity (p ≤ 0.5.

  19. Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome

    International Nuclear Information System (INIS)

    Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex- and activity-matched control subjects to assess the aerobic capacity. We performed 31phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO2; 34.1±6.2 vs. 41.4±8.4 ml kg-1 min-1, P-1 min-1, P2 (r=-0.64) and AT (r=-0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO2 (r=-0.47) and AT (r=-0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r=0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism. (author)

  20. Effects of extracellular polymer substances on aerobic granulation in sequencing batch reactors

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-ping; LIU Li-li; YAO Jie; SUN Li-xin; CAI Wei-min

    2009-01-01

    The effects of extracellular polymeric substances (EPS) on aerobic granulation in sequencing batch reactors (SBR) were investigated by evaluating the EPS content, and the relationship between EPS composition and surface properties of glucose-fed aerobic granules. The results show that aerobic granular sludge contains more EPS than seed sludge, and it is about 47 mg/gMLSS. Corresponding to the changes of EPS, the surface charge of microorganisms in granules increases from -0. 732 to -0. 845 meq/gMLSS, whereas the hydrophobicry changes significantly from 48.46% to 73. 16%. It is obviously that changes of EPS in sludge alter the negative surface charge and hydrophobieity of microorganisms in granules, enhance the polymeric interaction and promote the aerobic granulation. Moreover, EPS can serve as carbon and energy reserves in granulation, thus the growth between the interior and exterior bacteria is balanced, and the integrality of granules is maintained.SEM observation of the granules exhibits that EPS in granules are ropy ; by mixing with bacteria, compact matrix structure can be formed. The distribution of EPS in granules profiles the importance of EPS storage. It can be concluded that EPS play a crucial role in aerobic granulation.

  1. Occurrence and Fate of Trace Contaminants during Aerobic and Anaerobic Sludge Digestion and Dewatering.

    Science.gov (United States)

    Guerra, Paula; Kleywegt, Sonya; Payne, Michael; Svoboda, M Lewina; Lee, Hing-Biu; Reiner, Eric; Kolic, Terry; Metcalfe, Chris; Smyth, Shirley Anne

    2015-07-01

    Digestion of municipal wastewater biosolids is a necessary prerequisite to their beneficial use in land application, in order to protect public health and the receiving environment. In this study, 13 pharmaceuticals and personal care products (PPCPs), 11 musks, and 17 polybrominated diphenyl ethers were analyzed in 84 samples including primary sludge, waste activated sludge, digested biosolids, dewatered biosolids, and dewatering centrate or filtrate collected from five wastewater treatment plants with aerobic or anaerobic digestion. Aerobic digestion processes were sampled during both warm and cold temperatures to analyze seasonal differences. Among the studied compounds, triclosan, triclocarban, galaxolide, and BDE-209 were the substances most frequently detected under different treatment processes at levels up to 30,000 ng/g dry weight. Comparing aerobic and anaerobic digestion, it was observed that the levels of certain PPCPs and musks were significantly higher in anaerobically digested biosolids, relative to the residues from aerobic digestion. Therefore, aerobic digestion has the potential advantage of reducing levels of PPCPs and musks. On the other hand, anaerobic digestion has the advantage of recovering energy from the biosolids in the form of combustible gases while retaining the nutrient and soil conditioning value of this resource. PMID:26437100

  2. Anaerobic Metabolism: Linkages to Trace Gases and Aerobic Processes

    Science.gov (United States)

    Megonigal, J. P.; Hines, M. E.; Visscher, P. T.

    2003-12-01

    Life evolved and flourished in the absence of molecular oxygen (O2). As the O2 content of the atmosphere rose to the present level of 21% beginning about two billion years ago, anaerobic metabolism was gradually supplanted by aerobic metabolism. Anaerobic environments have persisted on Earth despite the transformation to an oxidized state because of the combined influence of water and organic matter. Molecular oxygen diffuses about 104 times more slowly through water than air, and organic matter supports a large biotic O2 demand that consumes the supply faster than it is replaced by diffusion. Such conditions exist in wetlands, rivers, estuaries, coastal marine sediments, aquifers, anoxic water columns, sewage digesters, landfills, the intestinal tracts of animals, and the rumen of herbivores. Anaerobic microsites are also embedded in oxic environments such as upland soils and marine water columns. Appreciable rates of aerobic respiration are restricted to areas that are in direct contact with air or those inhabited by organisms that produce O2.Rising atmospheric O2 reduced the global area of anaerobic habitat, but enhanced the overall rate of anaerobic metabolism (at least on an area basis) by increasing the supply of electron donors and acceptors. Organic carbon production increased dramatically, as did oxidized forms of nitrogen, manganese, iron, sulfur, and many other elements. In contemporary anaerobic ecosystems, nearly all of the reducing power is derived from photosynthesis, and most of it eventually returns to O2, the most electronegative electron acceptor that is abundant. This photosynthetically driven redox gradient has been thoroughly exploited by aerobic and anaerobic microorganisms for metabolism. The same is true of hydrothermal vents (Tunnicliffe, 1992) and some deep subsurface environments ( Chapelle et al., 2002), where thermal energy is the ultimate source of the reducing power.Although anaerobic habitats are currently a small fraction of Earth

  3. Reflections on Psychotherapy and Aerobic Exercise.

    Science.gov (United States)

    Silverman, Wade

    This document provides a series of reflections by a practicing psychologist on the uses of aerobic workouts in psychotherapy. Two case histories are cited to illustrate the contention that the mode of exercise, rather than simply its presence or absence, is the significant indicator of a patient's emotional well-being or psychopathology. The first…

  4. Glycogen metabolism in aerobic mixed cultures

    DEFF Research Database (Denmark)

    Dircks, Klaus; Beun, J.J.; van Loosdrecht, M.C.M.;

    2001-01-01

    In this study, the metabolism of glycogen storage and consumption in mixed cultures under aerobic conditions is described. The experimental results are used to calibrate a metabolic model, which as sole stoichiometric variables has the efficiency of oxidative phosphorylation (delta) and maintenan...

  5. The plant mitochondrial carrier family: functional and evolutionary aspects

    OpenAIRE

    Ilka eHaferkamp; Stephan eSchmitz-Esser

    2012-01-01

    Mitochondria play a key role in respiration and energy production and are involved in multiple eukaryotic but also in several plant specific metabolic pathways. Solute carriers in the inner mitochondrial membrane connect the internal metabolism with that of the surrounding cell. Because of their common basic structure, these transport proteins affiliate to the mitochondrial carrier family (MCF). Generally, MCF proteins consist of six membrane-spanning helices, exhibit typical conserved domain...

  6. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements

    OpenAIRE

    Nicolson, Garth L.

    2014-01-01

    Loss of function in mitochondria, the key organelle responsible for cellular energy production, can result in the excess fatigue and other symptoms that are common complaints in almost every chronic disease. At the molecular level, a reduction in mitochondrial function occurs as a result of the following changes: (1) a loss of maintenance of the electrical and chemical transmembrane potential of the inner mitochondrial membrane, (2) alterations in the function of the electron transport chain,...

  7. Role of mitochondrial lipids in guiding fission and fusion

    OpenAIRE

    Frohman, Michael A.

    2014-01-01

    Clinically-important links have been established between mitochondrial function and cardiac physiology and disease in the context of signaling mechanisms, energy production, and muscle cell development. The proteins and processes that drive mitochondrial fusion and fission are now known to have emergent functions in intracellular calcium homeostasis, apoptosis, vascular smooth muscle cell proliferation, myofibril organization, and Notch-driven cell differentiation, all key issues in cardiac d...

  8. Loss of the SIN3 transcriptional corepressor results in aberrant mitochondrial function

    Directory of Open Access Journals (Sweden)

    Hüttemann Maik

    2010-07-01

    Full Text Available Abstract Background SIN3 is a transcriptional repressor protein known to regulate many genes, including a number of those that encode mitochondrial components. Results By monitoring RNA levels, we find that loss of SIN3 in Drosophila cultured cells results in up-regulation of not only nuclear encoded mitochondrial genes, but also those encoded by the mitochondrial genome. The up-regulation of gene expression is accompanied by a perturbation in ATP levels in SIN3-deficient cells, suggesting that the changes in mitochondrial gene expression result in altered mitochondrial activity. In support of the hypothesis that SIN3 is necessary for normal mitochondrial function, yeast sin3 null mutants exhibit very poor growth on non-fermentable carbon sources and show lower levels of ATP and reduced respiration rates. Conclusions The findings that both yeast and Drosophila SIN3 affect mitochondrial activity suggest an evolutionarily conserved role for SIN3 in the control of cellular energy production.

  9. Is cell aging caused by respiration-dependent injury to the mitochondrial genome

    Science.gov (United States)

    Fleming, J. E.; Yengoyan, L. S.; Miquel, J.; Cottrell, S. F.; Economos, A. C.

    1982-01-01

    Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article, the hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells is expanded. It is maintained that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and, therefore, of organismic performance.

  10. Muscle-Specific Loss of Apoptosis-Inducing Factor Leads to Mitochondrial Dysfunction, Skeletal Muscle Atrophy, and Dilated Cardiomyopathy

    OpenAIRE

    Joza, Nicholas; Oudit, Gavin Y.; Brown, Doris; Bénit, Paule; Kassiri, Zamaneh; Vahsen, Nicola; Benoit, Loralyn; Patel, Mikin M.; Nowikovsky, Karin; Vassault, Anne; Backx, Peter H; Wada, Teiji; Kroemer, Guido; Rustin, Pierre; Penninger, Josef M.

    2005-01-01

    Cardiac and skeletal muscle critically depend on mitochondrial energy metabolism for their normal function. Recently, we showed that apoptosis-inducing factor (AIF), a mitochondrial protein implicated in programmed cell death, plays a role in mitochondrial respiration. However, the in vivo consequences of AIF-regulated mitochondrial respiration resulting from a loss-of-function mutation in Aif are not known. Here, we report tissue-specific deletion of Aif in the mouse. Mice in which Aif has b...

  11. EFFECTS OF AQUA AEROBICS AND FLOOR AEROBICS ON BREATH HOLDING TIME AMONG SCHOOL GIRLS

    OpenAIRE

    P.V. Shelvam; S. Arunadevi

    2013-01-01

    The purpose of the study was to find out the effects of aqua aerobics and floor aerobics on breath holding time among school girls. To achieve this purpose of the study, ninety school girls were selected as subjects who were studied Cornation Higher Secondary School, Sivakasi. The selected subjects were aged between 15 to 17 years. The selected subjects were randomly divided into three groups of 30 subjects each group. Group one acted as experimental group I and group two acted as experimenta...

  12. The interplay between aerobic metabolism and antipredator performance: vigilance is related to recovery rate after exercise

    Directory of Open Access Journals (Sweden)

    Shaun Steven Killen

    2015-04-01

    Full Text Available When attacked by a predator, fish respond with a sudden fast-start motion away from the threat. Although this anaerobically-powered swimming necessitates a recovery phase which is fuelled aerobically, little is known about links between escape performance and aerobic traits such as aerobic scope or recovery time after exhaustive exercise. Slower recovery ability or a reduced aerobic scope could make some individuals less likely to engage in a fast-start response or display reduced performance. Conversely, increased vigilance in some individuals could permit faster responses to an attack but also increase energy demand and prolong recovery after anaerobic exercise. We examined how aerobic scope and the ability to recover from anaerobic exercise relates to differences in fast-start escape performance in juvenile golden grey mullet at different acclimation temperatures. Individuals were acclimated to either 18, 22, or 26oC, then measured for standard and maximal metabolic rates and aerobic scope using intermittent flow respirometry. Anaerobic capacity and the time taken to recover after exercise were also assessed. Each fish was also filmed during a simulated attack to determine response latency, maximum speed and acceleration, and turning rate displayed during the escape response. Across temperatures, individuals with shorter response latencies during a simulated attack are those with the longest recovery time after exhaustive anaerobic exercise. Because a short response latency implies high preparedness to escape, these results highlight the trade-off between the increased vigilance and metabolic demand, which leads to longer recovery times in fast reactors. These results improve our understanding of the intrinsic physiological traits that generate inter-individual variability in escape ability, and emphasise that a full appreciation of trade-offs associated with predator avoidance and energy balance must include energetic costs associated with

  13. Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA.

    Directory of Open Access Journals (Sweden)

    Philippe A Parone

    Full Text Available Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, the role of mitochondrial fission in homeostasis of the organelle is still unknown. Here we report that preventing mitochondrial fission, by down-regulating expression of Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of mitochondrial respiration coupled to an increase in the levels of cellular reactive oxygen species (ROS. At the cellular level, mitochondrial dysfunction resulting from the lack of fission leads to a drop in the levels of cellular ATP, an inhibition of cell proliferation and an increase in autophagy. In conclusion, we propose that mitochondrial fission is required for preservation of mitochondrial function and thereby for maintenance of cellular homeostasis.

  14. p63 supports aerobic respiration through hexokinase II.

    Science.gov (United States)

    Viticchiè, Guiditta; Agostini, Massimiliano; Lena, Anna Maria; Mancini, Mara; Zhou, Huiqing; Zolla, Lello; Dinsdale, David; Saintigny, Gaelle; Melino, Gerry; Candi, Eleonora

    2015-09-15

    Short p63 isoform, ΔNp63, is crucial for epidermis formation, and it plays a pivotal role in controlling the turnover of basal keratinocytes by regulating the expression of a subset of genes involved in cell cycle and cell adhesion programs. The glycolytic enzyme hexokinase 2 (HK2) represents the first step of glucose utilization in cells. The family of HKs has four isoforms that differ mainly in their tissue and subcellular distribution. The preferential mitochondrial localization of HK2 at voltage-dependent anion channels provides access to ATP generated by oxidative phosphorylation and generates an ADP/ATP recycling mechanism to maintain high respiration rates and low electron leak. Here, we report that ΔNp63 depletion in human keratinocytes impairs mitochondrial basal respiration and increases mitochondrial membrane polarization and intracellular reactive oxygen species. We show ΔNp63-dependent regulation of HK2 expression, and we use ChIP, validated by p63-Chip sequencing genomewide profiling analysis, and luciferase assays to demonstrate the presence of one p63-specific responsive element within the 15th intronic region of the HK2 gene, providing evidence of a direct interaction. Our data support the notion of ΔNp63 as a master regulator in epithelial cells of a combined subset of molecular mechanisms, including cellular energy metabolism and respiration. The ΔNp63-HK2 axis is also present in epithelial cancer cells, suggesting that ΔNp63 could participate in cancer metabolic reprogramming. PMID:26324887

  15. Estimation of Aerobic Capacity (VO2-max and Physical Work Capacity in Laborers

    Directory of Open Access Journals (Sweden)

    Sedeghe Hosseinabadi

    2013-06-01

    Full Text Available Introduction: Measurement of Maximum aerobic capacity (VO2-max is important in physiologically fitting the laborers to the job. This study was conducted to estimate the aerobic capacity and physical work capacity (PWC of workers of galvanize department of Semnan rolling pipe Company and also determine the relative frequency of workers whom their jobs were proportional to their physical work capacity . Methods: 50 male workers of Semnan rolling pipe company were selected randomly to participate in this cross-sectional study. Tuxworth & shahnavaz methods were applied to measure instances VO2-MAX. Independent-Sample t-test and correlation technique were used to analysis the data by SPSS software. Results: Average maximum aerobic capacity of workers was 2.88± .033 liters per minute and the average of physical work capacity was 4.76 ± 0.54 kilocalories per minute. There was a significant relationship between body mass index and aerobic capacity. The result showed that 36 percent of subjects expend more energy than their physical work capacity to perform their duties during the work time. Conclusion: According to the ILO classification, the average physical work capacity of the workers fall into a category of light energy;accordingly, on average, these workers had physical ability to performe less or lighter duties. More than one-third of these workers need to undergo job modification or to change their present job to a job with less energy consumption.

  16. Mitochondrial Adenine Nucleotide Transport and Cardioprotection

    OpenAIRE

    Das, Samarjit; Steenbergen, Charles

    2011-01-01

    Mitochondria are highly metabolically active cell organelles that not only act as the powerhouse of the cell by supplying energy through ATP production, but also play a destructive role by initiating cell death pathways. Growing evidence recognizes that mitochondrial dysfunction is one of the major causes of cardiovascular disease. Under de-energized conditions, slowing of adenine nucleotide transport in and out of the mitochondria significantly attenuates myocardial ischemia-reperfusion inju...

  17. Review: Mitochondrial Defects in Breast Cancer

    OpenAIRE

    Salgado, J.; Honorato, B. (Beatriz); Garcia-Foncillas, J

    2008-01-01

    Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of its high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Breast cancer is the most frequent cancer type among women in the world and, although exhaustive research has been done on nuclear DNA changes, several studies describe ...

  18. Metabolic Determinants of Mitochondrial Function in Oocytes.

    Science.gov (United States)

    Seidler, Emily A; Moley, Kelle H

    2015-11-01

    Mitochondrial production of cellular energy is essential to oocyte function, zygote development and successful continuation of pregnancy. This review focuses on several key functions of healthy oocyte mitochondria and the effect of pathologic states such as aging, oxidative stress and apoptosis on these functions. The effect of these abnormal conditions is presented in terms of clinical presentations, specifically maternal obesity, diminished ovarian reserve and assisted reproductive technologies.

  19. Ecology of aerobic anoxygenic phototrophs in aquatic environments.

    Science.gov (United States)

    Koblížek, Michal

    2015-11-01

    Recognition of the environmental role of photoheterotrophic bacteria has been one of the main themes of aquatic microbiology over the last 15 years. Aside from cyanobacteria and proteorhodopsin-containing bacteria, aerobic anoxygenic phototrophic (AAP) bacteria are the third most numerous group of phototrophic prokaryotes in the ocean. This functional group represents a diverse assembly of species which taxonomically belong to various subgroups of Alpha-, Beta- and Gammaproteobacteria. AAP bacteria are facultative photoheterotrophs which use bacteriochlorophyll-containing reaction centers to harvest light energy. The light-derived energy increases their bacterial growth efficiency, which provides a competitive advantage over heterotrophic species. Thanks to their enzymatic machinery AAP bacteria are active, rapidly growing organisms which contribute significantly to the recycling of organic matter. This chapter summarizes the current knowledge of the ecology of AAP bacteria in aquatic environments, implying their specific role in the microbial loop.

  20. Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment

    Directory of Open Access Journals (Sweden)

    Daniel A. Rossignol

    2008-01-01

    Full Text Available Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD without the classic features associated with mitochondrial disease. MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environ-mental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress. MtD and oxidative stress may also explain the high male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions. Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT represent supported and rationale approaches. The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

  1. Sealing the Mitochondrial Respirasome

    OpenAIRE

    Winge, Dennis R.

    2012-01-01

    The mitochondrial respiratory chain is organized within an array of supercomplexes that function to minimize the generation of reactive oxygen species (ROS) during electron transfer reactions. Structural models of supercomplexes are now known. Another recent advance is the discovery of non-OXPHOS complex proteins that appear to adhere to and seal the individual respiratory complexes to form stable assemblages that prevent electron leakage. This review highlights recent advances in our underst...

  2. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  3. Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.

    Directory of Open Access Journals (Sweden)

    Yilin Cao

    Full Text Available T lymphocytes (T cells undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.

  4. Mitochondrial DNA Damage and Animal Longevity: Insights from Comparative Studies

    Directory of Open Access Journals (Sweden)

    Reinald Pamplona

    2011-01-01

    Full Text Available Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA. ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

  5. Comparison of sidestream treatment technologies: post aerobic digestion and Anammox.

    Science.gov (United States)

    Bauer, Heidi; Johnson, Thomas D; Johnson, Bruce R; Oerke, David; Graziano, Steven

    2016-01-01

    Post aerobic digestion (PAD) and anaerobic ammonium oxidation (Anammox) are sidestream treatment technologies which are both excellent options for the reduction of nitrogen recycled back to the liquid stream without the need for supplemental carbon or alkalinity. However, the achievement of this goal is where the similarities between the two technologies end. PAD is an advanced digestion process where aerobic digestion is designed to follow anaerobic digestion. Other benefits of PAD include volatile solids reduction, odor reduction, and struvite formation reduction. Anammox harnesses a specific species of autotrophic bacteria that can help achieve partial nitritation/deammonification. Other benefits of Anammox include lower energy consumption due to requiring less oxygen compared with conventional nitrification. This manuscript describes the unique benefits and challenges of each technology. Example installations are presented with a narrative of how and why the technology was selected. A whole plant simulator is used to compare and contrast the mass balances and net present value costs on an 'apples to apples' basis. The discussion includes descriptions of conditions under which each technology would potentially be the most beneficial and cost-effective against a baseline facility without sidestream treatment. PMID:27232417

  6. Mitochondrial biogenesis of astrocytes is increased under experimental septic conditions

    Institute of Scientific and Technical Information of China (English)

    Wang Yang; Chen Zhijiang; Zhang Yu; Fang Suzhen; Zeng Qiyi

    2014-01-01

    Background Mitochondrial dysfunction has been reported to be one of the contributing factors of sepsis-associated encephalopathy (SAE).Mitochondrial biogenesis controls mitochondrial homeostasis and responds to changes in cellular energy demand.In addition,it is enhanced or decreased due to mitochondrial dysfunction during SAE.The aim of this study was to explore the changes of mitochondrial biogenesis of astrocytes under septic conditions.Methods Lipopolysaccharide (LPS; 50 ng/ml) and interferon-γ (IFN-γ; 200 U/ml) were incubated with astrocytes to model the effects of a septic insult on astrocytes in vitro.The mitochondrial ultrastructure and volume density were evaluated by transmission electron microscopy.Intracellular adenosine triphosphate (ATP) levels were detected by the firefly luciferase system.The expression of protein markers of mitochondrial biogenesis and the binding ability of mitochondrial transcription factor A (TFAM) were determined by western blot and electrophoretic mobility shift assays,respectively.The mitochondrial DNA (mtDNA) content was detected by real-time polymerase chain reaction.Results The number of mildly damaged mitochondria was found to be significantly greater after treatment for 6 hours,as compared with at 0 hour (P<0.05).The mitochondrial volume density was significantly elevated at 24 hours,as compared with at 0 hour (P<0.05).The ATP levels at 6 hours,12 hours,and 24 hours were significantly greater than those at 0 hour (P<0.05).The protein markers of mitochondrial biogenesis were significantly increased at 6 hours and 12 hours,as compared with at 0 hour (P<0.05).The TFAM binding activity was not significantly changed among the four time points analyzed.The mtDNA contents were significantly increased at 12 hours and 24 hours,as compared with at 0 hour (P<0.05).Conclusions Under septic conditions,mitochonddal biogenesis of astrocytes increased to meet the high-energy demand and to promote mitochondrial recovery

  7. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    Directory of Open Access Journals (Sweden)

    Hirotaka Yamamoto

    2016-01-01

    Full Text Available Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders.

  8. Estrogen regulation of glucose metabolism and mitochondrial function: therapeutic implications for prevention of Alzheimer's disease.

    Science.gov (United States)

    Brinton, Roberta Diaz

    2008-01-01

    Estrogen-induced signaling pathways in hippocampal and cortical neurons converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis and citric acid cycle-driven oxidative phosphorylation and ATP generation. Data derived from experimental and clinical paradigms investigating estrogen intervention in healthy systems and prior to neurodegenerative insult indicate enhanced neural defense and survival through maintenance of calcium homeostasis, enhanced glycolysis coupled to the citric acid cycle (aerobic glycolysis), sustained and enhanced mitochondrial function, protection against free radical damage, efficient cholesterol trafficking and beta amyloid clearance. The convergence of E(2) mechanisms of action onto mitochondrial is also a potential point of vulnerability when activated in a degenerating neural system and could exacerbate the degenerative processes through increased load on dysregulated calcium homeostasis. The data indicate that as the continuum of neurological health progresses from healthy to unhealthy so too do the benefits of estrogen or hormone therapy. If neurons are healthy at the time of estrogen exposure, their response to estrogen is beneficial for both neuronal survival and neurological function. In contrast, if neurological health is compromised, estrogen exposure over time exacerbates neurological demise. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess the disparities in outcomes across the basic to clinical domains of scientific inquiry and on which to predict future applications of estrogen and hormone therapeutic interventions sustain neurological health and to prevent age-associated neurodegenerative diseases such as Alzheimer's. Overall, E(2) promotes the energetic capacity of brain mitochondria by maximizing aerobic glycolysis (oxidative phosphorylation coupled to pyruvate metabolism). The enhanced aerobic glycolysis in the aging brain would be predicted

  9. The mitochondrial complexome of Medicago truncatula

    Directory of Open Access Journals (Sweden)

    Leonard Muriithi Kiirika

    2013-04-01

    Full Text Available Legumes (Fabaceae, Leguminosae are unique in their ability to carry out an elaborate endosymbiotic nitrogen fixation process with rhizobia proteobacteria. The symbiotic nitrogen fixation enables the host plants to grow almost independently of any other nitrogen source. Establishment of symbiosis requires adaptations of the host cellular metabolism, here foremost of the energy metabolism mainly taking place in mitochondria. Since the early 1990s, the galegoid legume Medicago truncatula Gaertn. is a well-established model for studying legume biology, but little is known about the protein complement of mitochondria from this species. An initial characterization of the mitochondrial proteome of M. truncatula (Jemalong A17 was published recently. In the frame of this study, mitochondrial protein complexes were characterized using 2D BN / SDS PAGE. From 139 detected spots, the "first hit" (= most abundant proteins of 59 spots were identified by mass spectrometry. Here, we present a comprehensive analysis of the mitochondrial complexome (the protein complex proteome of M. truncatula via 2D BN / SDS PAGE in combination with high sensitive MS protein identification. In total, 1,485 proteins were identified within 158 gel spots, representing 467 unique proteins. Data evaluation by the novel GelMap annotation tool allowed recognition of protein complexes of low abundance. Overall, at least 36 mitochondrial protein complexes were found. To our knowledge several of these complexes were described for the first time in Medicago. The data set is accessible under http://www.gelmap.de/medicago/. The mitochondrial protein complex proteomes of Arabidopsis (available at http://www.gelmap.de/arabidopsis/ and Medicago are compared.

  10. Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

    Science.gov (United States)

    Machado, Alencar Kolinski; Pan, Alexander Yongshuai; da Silva, Tatiane Morgana; Duong, Angela; Andreazza, Ana Cristina

    2016-08-01

    Mitochondrial dysfunction is commonly observed in bipolar disorder (BD) and schizophrenia (SCZ) and may be a central feature of psychosis. These illnesses are complex and heterogeneous, which is reflected by the complexity of the processes regulating mitochondrial function. Mitochondria are typically associated with energy production; however, dysfunction of mitochondria affects not only energy production but also vital cellular processes, including the formation of reactive oxygen species, cell cycle and survival, intracellular Ca(2+) homeostasis, and neurotransmission. In this review, we characterize the upstream components controlling mitochondrial function, including 1) mutations in nuclear and mitochondrial DNA, 2) mitochondrial dynamics, and 3) intracellular Ca(2+) homeostasis. Characterizing and understanding the upstream factors that regulate mitochondrial function is essential to understand progression of these illnesses and develop biomarkers and therapeutics. PMID:27310240

  11. A mitochondrial CO2-adenylyl cyclase-cAMP signalosome controls yeast normoxic cytochrome c oxidase activity.

    Science.gov (United States)

    Hess, Kenneth C; Liu, Jingjing; Manfredi, Giovanni; Mühlschlegel, Fritz A; Buck, Jochen; Levin, Lonny R; Barrientos, Antoni

    2014-10-01

    Mitochondria, the major source of cellular energy in the form of ATP, respond to changes in substrate availability and bioenergetic demands by employing rapid, short-term, metabolic adaptation mechanisms, such as phosphorylation-dependent protein regulation. In mammalian cells, an intramitochondrial CO2-adenylyl cyclase (AC)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway regulates aerobic energy production. One target of this pathway involves phosphorylation of cytochrome c oxidase (COX) subunit 4-isoform 1 (COX4i1), which modulates COX allosteric regulation by ATP. However, the role of the CO2-sAC-cAMP-PKA signalosome in regulating COX activity and mitochondrial metabolism and its evolutionary conservation remain to be fully established. We show that in Saccharomyces cerevisiae, normoxic COX activity measured in the presence of ATP is 55% lower than in the presence of ADP. Moreover, the adenylyl cyclase Cyr1 activity is present in mitochondria, and it contributes to the ATP-mediated regulation of COX through the normoxic subunit Cox5a, homologue of human COX4i1, in a bicarbonate-sensitive manner. Furthermore, we have identified 2 phosphorylation targets in Cox5a (T65 and S43) that modulate its allosteric regulation by ATP. These residues are not conserved in the Cox5b-containing hypoxic enzyme, which is not regulated by ATP. We conclude that across evolution, a CO2-sAC-cAMP-PKA axis regulates normoxic COX activity.

  12. The effect of chronic exposure to high palmitic acid concentrations on the aerobic metabolism of human endothelial EA.hy926 cells.

    Science.gov (United States)

    Broniarek, Izabela; Koziel, Agnieszka; Jarmuszkiewicz, Wieslawa

    2016-09-01

    A chronic elevation of circulating free fatty acids (FFAs) is associated with diseases like obesity or diabetes and can lead to lipotoxicity. The goals of this study were to assess the influence of chronic exposure to high palmitic acid (PAL) levels on mitochondrial respiratory functions in endothelial cells and isolated mitochondria. Human umbilical vein endothelial cells (EA.hy926 line) were grown for 6 days in a medium containing either 100 or 150 μM PAL. Growth at high PAL concentrations induced a considerable increase in fatty acid-supplied respiration and a reduction of mitochondrial respiration during carbohydrate and glutamine oxidation. High PAL levels elevated intracellular and mitochondrial superoxide generation; increased inflammation marker, acyl-coenzyme A (CoA) dehydrogenase, uncoupling protein 2 (UCP2), and superoxide dismutase 2 expression; and decreased hexokinase I and pyruvate dehydrogenase expression. No change in aerobic respiration capacity was observed, while fermentation was decreased. In mitochondria isolated from high PAL-treated cells, an increase in the oxidation of palmitoylcarnitine, a decrease in the oxidation of pyruvate, and an increase in UCP2 activity were observed. Our results demonstrate that exposure to high PAL levels induces a shift in endothelial aerobic metabolism toward the oxidation of fatty acids. Increased levels of PAL caused impairment and uncoupling of the mitochondrial oxidative phosphorylation system. Our data indicate that FFAs significantly affect endothelial oxidative metabolism, reactive oxygen species (ROS) formation, and cell viability and, thus, might contribute to endothelial and vascular dysfunction. PMID:27417103

  13. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    OpenAIRE

    Rooijers, Koos; Loayza-Puch, Fabricio; Nijtmans, Leo G.; Agami, Reuven

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations often affect components of the mitochondrial translation machinery. Here we perform ribosome profiling to measure mitochondrial translation at nucleotide resolution. Using a protocol optimized for the...

  14. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria

    OpenAIRE

    cunha-oliveira, teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J.; Oliveira, Catarina R.; Santos, Maria S.

    2013-01-01

    Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand ...

  15. Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Gejl, Kasper D; Hey-Mogensen, Martin;

    2016-01-01

    that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents and improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements. This article is protected by copyright. All rights reserved.......-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose...

  16. Experimental evidence for aerobic bio-denitrification

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Nitrate pollution of groundwater is paid more and more attention for its hazardous to environments and human health. A strain of DN11 was isolated from soil and used in the laboratory columns filled with various media for nitrate removal. The experimental results showed that DN11could reduce nitrate at different rates in different media under the aerobic condition. The mechanism for nitrate removal with DN11 is explained meanwhile.

  17. Acute effects of aerobic exercise promote learning

    OpenAIRE

    Renza Perini; Marta Bortoletto; Michela Capogrosso; Anna Fertonani; Carlo Miniussi

    2016-01-01

    The benefits that physical exercise confers on cardiovascular health are well known, whereas the notion that physical exercise can also improve cognitive performance has only recently begun to be explored and has thus far yielded only controversial results. In the present study, we used a sample of young male subjects to test the effects that a single bout of aerobic exercise has on learning. Two tasks were run: the first was an orientation discrimination task involving the primary visual cor...

  18. Bee Pollen Improves Muscle Protein and Energy Metabolism in Malnourished Old Rats through Interfering with the Mtor Signaling Pathway and Mitochondrial Activity

    Directory of Open Access Journals (Sweden)

    Jérôme Salles

    2014-12-01

    Full Text Available Although the management of malnutrition is a priority in older people, this population shows a resistance to refeeding. Fresh bee pollen contains nutritional substances of interest for malnourished people. The aim was to evaluate the effect of fresh bee pollen supplementation on refeeding efficiency in old malnourished rats. Male 22-month-old Wistar rats were undernourished by reducing food intake for 12 weeks. The animals were then renourished for three weeks with the same diet supplemented with 0%, 5% or 10% of fresh monofloral bee pollen. Due to changes in both lean mass and fat mass, body weight decreased during malnutrition and increased after refeeding with no between-group differences (p < 0.0001. Rats refed with the fresh bee pollen-enriched diets showed a significant increase in muscle mass compared to restricted rats (p < 0.05. The malnutrition period reduced the muscle protein synthesis rate and mTOR/p70S6kinase/4eBP1 activation, and only the 10%-pollen diet was able to restore these parameters. Mitochondrial activity was depressed with food restriction and was only improved by refeeding with the fresh bee pollen-containing diets. In conclusion, refeeding diets that contain fresh monofloral bee pollen improve muscle mass and metabolism in old, undernourished rats.

  19. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity.

    Science.gov (United States)

    Szeto, H H; Birk, A V

    2014-12-01

    The mitochondrial electron transport chain (ETC) plays a central role in energy generation in the cell. Mitochondrial dysfunctions diminish adenosine triphosphate (ATP) production and result in insufficient energy to maintain cell function. As energy output declines, the most energetic tissues are preferentially affected. To satisfy cellular energy demands, the mitochondrial ETC needs to be able to elevate its capacity to produce ATP at times of increased metabolic demand or decreased fuel supply. This mitochondrial plasticity is reduced in many age-associated diseases. In this review, we describe the serendipitous discovery of a novel class of compounds that selectively target cardiolipin on the inner mitochondrial membrane to optimize efficiency of the ETC and thereby restore cellular bioenergetics in aging and diverse disease models, without any effect on the normal healthy organism. The first of these compounds, SS-31, is currently in multiple clinical trials. PMID:25188726

  20. The Effect of Aerobic Exercise under High Temperature and Humidity and General Environment on Wrestling Athletes’ Energy Metabolism and Strength Quality%高温高湿对比一般环境有氧运动对摔跤运动员能量代谢和力量素质的影响

    Institute of Scientific and Technical Information of China (English)

    周祎; 赵凡

    2015-01-01

    目的:通过高温高湿及一般环境有氧运动与减体重相关指标的测试和评价,了解不同环境有氧运动对机体减体重效果的影响。方法:以北京市8名男子自由式摔跤运动员作为研究对象,测试不同环境有氧运动(50 min65%VO2 max强度)前后体重、等速肌力、能量代谢、反应时等指标。结果:相同生理负荷下在高温高湿和常温常湿两种环境中分别进行一次性有氧运动50 min ,高温高湿下体重下降1.91%,幅度略大于常温常湿;高温高湿组运动过程中能量代谢较常温常湿组高1.52%,运动后2 h能量消耗较常温常湿组高0.95%,睡眠8 h的能量代谢较常温常湿组高14.86%,具有显著性差异( P<0.05);运动员能够耐受在不同环境温度进行的减控重训练,主观上能够接受(33℃、60%)的热环境;在不同环境中进行有氧运动后,运动员的最大力量、疲劳指数和反应时没有显著性变化,最大峰值力矩、平均功率在不同环境下有氧运动后均出现下降趋势,反应时在不同环境运动后时间有所缩短,表明在不同的环境下进行一次性有氧运动对力量素质、肌肉耐力和反应能力没有表现出显著的不利影响。结论:高温高湿环境中通过有氧运动进行减体重具有相对较好的效果,在减体重期间,为减少力量的丢失,在进行减体重的有氧训练过程中应适当增加力量训练。%Objective :Through testing and evaluating on related indexes of weigth reduction and aerobic exercise under high temperature and humidity and general environment ,this paper tries to finds out the effects of aerobic exercise at different environment on weight reduction .Meth‐od :Taking 8 male freestyle wrestling athletes from Beijng as research objects to test their body weight ,isokinetic strength ,energy metabolism ,reaction time before and after the aerobic exer

  1. Nitrification and aerobic denitrification in anoxic-aerobic sequencing batch reactor.

    Science.gov (United States)

    Alzate Marin, Juan C; Caravelli, Alejandro H; Zaritzky, Noemí E

    2016-01-01

    The aim of this study was to evaluate the feasibility of achieving nitrogen (N) removal using a lab-scale sequencing batch reactor (SBR) exposed to anoxic/aerobic (AN/OX) phases, focusing to achieve aerobic denitrification. This process will minimize emissions of N2O greenhouse gas. The effects of different operating parameters on the reactor performance were studied: cycle duration, AN/OX ratio, pH, dissolved oxygen concentration (DOC), and organic load. The highest inorganic N removal (NiR), close to 70%, was obtained at pH=7.5, low organic load (440mgCOD/(Lday)) and high aeration given by 12h cycle, AN/OX ratio=0.5:1.0 and DOC higher than 4.0mgO2/L. Nitrification followed by high-rate aerobic denitrification took place during the aerobic phase. Aerobic denitrification could be attributed to Tetrad-forming organisms (TFOs) with phenotype of glycogen accumulating organisms using polyhydroxyalkanoate and/or glycogen storage. The proposed AN/OX system constitutes an eco-friendly N removal process providing N2 as the end product. PMID:26512862

  2. Mitochondrial dynamics and cell death in heart failure.

    Science.gov (United States)

    Marín-García, José; Akhmedov, Alexander T

    2016-03-01

    The highly regulated processes of mitochondrial fusion (joining), fission (division) and trafficking, collectively called mitochondrial dynamics, determine cell-type specific morphology, intracellular distribution and activity of these critical organelles. Mitochondria are critical for cardiac function, while their structural and functional abnormalities contribute to several common cardiovascular diseases, including heart failure (HF). The tightly balanced mitochondrial fusion and fission determine number, morphology and activity of these multifunctional organelles. Although the intracellular architecture of mature cardiomyocytes greatly restricts mitochondrial dynamics, this process occurs in the adult human heart. Fusion and fission modulate multiple mitochondrial functions, ranging from energy and reactive oxygen species production to Ca(2+) homeostasis and cell death, allowing the heart to respond properly to body demands. Tightly controlled balance between fusion and fission is of utmost importance in the high energy-demanding cardiomyocytes. A shift toward fission leads to mitochondrial fragmentation, while a shift toward fusion results in the formation of enlarged mitochondria and in the fusion of damaged mitochondria with healthy organelles. Mfn1, Mfn2 and OPA1 constitute the core machinery promoting mitochondrial fusion, whereas Drp1, Fis1, Mff and MiD49/51 are the core components of fission machinery. Growing evidence suggests that fusion/fission factors in adult cardiomyocytes play essential noncanonical roles in cardiac development, Ca(2+) signaling, mitochondrial quality control and cell death. Impairment of this complex circuit causes cardiomyocyte dysfunction and death contributing to heart injury culminating in HF. Pharmacological targeting of components of this intricate network may be a novel therapeutic modality for HF treatment. PMID:26872674

  3. Inheritance of the yeast mitochondrial genome

    DEFF Research Database (Denmark)

    Piskur, Jure

    1994-01-01

    Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast......Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast...

  4. Combined effects of temperature acclimation and cadmium exposure on mitochondrial function in eastern oysters Crassostrea virginica gmelin (Bivalvia: Ostreidae).

    Science.gov (United States)

    Cherkasov, Anton S; Ringwood, Amy H; Sokolova, Inna M

    2006-09-01

    Cadmium and temperature have strong impacts on the metabolic physiology of aquatic organisms. To analyze the combined impact of these two stressors on aerobic capacity, effects of Cd exposure (50 microg/L) on mitochondrial function were studied in oysters (Crassostrea virginica) acclimated to 12 and 20 degrees C in winter and to 20 and 28 degrees C in fall. Cadmium exposure had different effects on mitochondrial bioenergetics of oysters depending on the acclimation temperature. In oysters acclimated to 12 degrees C, Cd exposure resulted in elevated intrinsic rates of mitochondrial oxidation, whereas at 28 degrees C, a rapid and pronounced decrease of mitochondrial oxidative capacity was found in Cd-exposed oysters. At the intermediate acclimation temperature (20 degrees C), effects of Cd exposure on intrinsic rates of mitochondrial oxidation were negligible. Degree of coupling significantly decreased in mitochondria from 28 degrees C-acclimated oysters but not in that from 12 degrees C- or 20 degrees C-acclimated oysters. Acclimation at elevated temperatures also increased sensitivity of oyster mitochondria to extramitochondrial Cd. Variation in mitochondrial membrane potential explained 41% of the observed variation in mitochondrial adenosine triphosphate synthesis and proton leak between different acclimation groups of oysters. Temperature-dependent sensitivity of metabolic physiology to Cd has significant implications for toxicity testing and for extrapolation of laboratory studies to field populations of aquatic poikilotherms, indicating the importance of taking into account the thermal regime of the environment. PMID:16986802

  5. Defective insulin signaling and mitochondrial dynamics in diabetic cardiomyopathy

    Science.gov (United States)

    Westermeier, Francisco; Navarro-Marquez, Mario; López-Crisosto, Camila; Bravo-Sagua, Roberto; Quiroga, Clara; Bustamante, Mario; Verdejo, Hugo E.; Zalaquett, Ricardo; Ibacache, Mauricio; Parra, Valentina; Castro, Pablo F.; Rothermel, Beverly A.; Hill, Joseph A.; Lavandero, Sergio

    2015-01-01

    Diabetic cardiomyopathy (DCM) is a common consequence of longstanding type 2 diabetes mellitus (T2DM) and encompasses structural, morphological, functional, and metabolic abnormalities in the heart. Myocardial energy metabolism depends on mitochondria, which must generate sufficient ATP to meet the high energy demands of the myocardium. Dysfunctional mitochondria are involved in the pathophysiology of diabetic heart disease. A large body of evidence implicates myocardial insulin resistance in the pathogenesis of DCM. Recent studies show that insulin signaling influences myocardial energy metabolism by impacting cardiomyocyte mitochondrial dynamics and function under physiological conditions. However, comprehensive understanding of molecular mechanisms linking insulin signaling and changes in the architecture of the mitochondrial network in diabetic cardiomyopathy is lacking. This review summarizes our current understanding of how defective insulin signaling impacts cardiac function in diabetic cardiomyopathy and discusses the potential role of mitochondrial dynamics. PMID:25686534

  6. Sealing the mitochondrial respirasome.

    Science.gov (United States)

    Winge, Dennis R

    2012-07-01

    The mitochondrial respiratory chain is organized within an array of supercomplexes that function to minimize the generation of reactive oxygen species (ROS) during electron transfer reactions. Structural models of supercomplexes are now known. Another recent advance is the discovery of non-OXPHOS complex proteins that appear to adhere to and seal the individual respiratory complexes to form stable assemblages that prevent electron leakage. This review highlights recent advances in our understanding of the structures of supercomplexes and the factors that mediate their stability.

  7. Effect of mitochondrial aconitase activity on energy synthesis during aging%衰老过程中线粒体顺乌头酸酶活性变化对能量合成的影响

    Institute of Scientific and Technical Information of China (English)

    叶薇; 陈赛慧; 郝东杰; 郑屹; 曹建明; 吕建新

    2013-01-01

    AIM:To investigate the effect of mitochondrial aconitase (ACO2) on energy synthesis during aging in male SD rats and D-galactose-induced cell aging model.METHODS:D-galactose at concentration of 55 mmoL was used to establish MRC-5 cell aging model.Intact mitochondria in the rat brain and MRC-5 cells were isolated by a sucrose density gradient centrifugation.The formation of NADPH was used to represent the ACO2 activity and determined by observation of the absorbance at 340 nm.Fluorescence quantitative PCR and Western blotting were applied to detected ACO2 expression.Superxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by the commercial assay kits.The tissue iron content was detected by ferrozine method.Mitochondrial membrane potential was detected by JC-1mitochondrial membrane potential detection kit.The content of ATP,ADP and AMP was measured by HPLC analysis,and the energy charge was then calculated by theformula.RESULTS:ACO2 activity and iron content presented age-related decline and increase,respectively,while the expression level of ACO2 kept stable.ACO2 activity significantly declined when the cells were treated with hydrogen peroxide at different concentrations.In the aging cells,SOD activity and ACO2activity were decreased and MDA content was increased significantly,while the expression level of ACO2 was unchanged.During aging,mitochondial membrane potential,ATP synthesis and energy charge presented significant reduction.CONCLUSION:The activity of ACO2,which is sensitive to oxidative stress,declines during aging,and may affect the efficiency of the Krebs cycle.At the same time,mitochondrial membrane potential decreases,thus reducing the energy synthesis in mitochondria.%目的:利用自然衰老雄性SD大鼠和D-半乳糖(D-Gal)诱导的细胞衰老模型,研究在衰老细胞中线粒体顺乌头酸酶(mitochondrial aconitase,ACO2)活性的变化及其对能量合成的影响.方法:利用55 mmol/L D-Gal

  8. Characteristics of Pb2+ biosorption with aerobic granular biomass

    Institute of Scientific and Technical Information of China (English)

    YAO Lei; YE ZhengFang; WANG ZhongYou; NI JinRen

    2008-01-01

    Experimental studies were conducted on the feasibility of aerobic granular biomass as a novel type of biosorbent for Pb2+ removal. The results show that the initial pH, Pb2+ concentration (C0) and biomass concentration (X0) affected the biosorption process significantly. Both the Freundlich and Langmuir isotherm models describe the biosorption process accurately, with correlation coefficients of 0.932 and 0.959 respectively. The Pb2+ biosorption kinetics is interpreted as having two stages, with the second stage described reasonably well by a Lagergren pseudo-second order model. Moreover, the surface change of granular biomass after the Pb2+ biosorption process appears to be caused by ion exchange and metal chelation according to the analysis results of Environmental Scanning Electron Microscopy (ESEM) and Energy Dispersive X-ray Spectroscopy (EDX).

  9. Biochemical diagnosis of mitochondrial disorders

    NARCIS (Netherlands)

    Rodenburg, R.J.T.

    2011-01-01

    Establishing a diagnosis in patients with a suspected mitochondrial disorder is often a challenge. Both knowledge of the clinical spectrum of mitochondrial disorders and the number of identified disease-causing molecular genetic defects are continuously expanding. The diagnostic examination of patie

  10. Muscle regeneration in mitochondrial myopathies

    DEFF Research Database (Denmark)

    Krag, T O; Hauerslev, S; Jeppesen, T D;

    2013-01-01

    Mitochondrial myopathies cover a diverse group of disorders in which ragged red and COX-negative fibers are common findings on muscle morphology. In contrast, muscle degeneration and regeneration, typically found in muscular dystrophies, are not considered characteristic features of mitochondrial...

  11. NDE1 and GSK3β Associate with TRAK1 and Regulate Axonal Mitochondrial Motility: Identification of Cyclic AMP as a Novel Modulator of Axonal Mitochondrial Trafficking.

    Science.gov (United States)

    Ogawa, Fumiaki; Murphy, Laura C; Malavasi, Elise L V; O'Sullivan, Shane T; Torrance, Helen S; Porteous, David J; Millar, J Kirsty

    2016-05-18

    Mitochondria are essential for neuronal function, providing the energy required to power neurotransmission, and fulfilling many important additional roles. In neurons, mitochondria must be efficiently transported to sites, including synapses, where their functions are required. Neurons, with their highly elongated morphology, are consequently extremely sensitive to defective mitochondrial trafficking which can lead to neuronal ill-health/death. We recently demonstrated that DISC1 associates with mitochondrial trafficking complexes where it associates with the core kinesin and dynein adaptor molecule TRAK1. We now show that the DISC1 interactors NDE1 and GSK3β also associate robustly with TRAK1 and demonstrate that NDE1 promotes retrograde axonal mitochondrial movement. GSK3β is known to modulate axonal mitochondrial motility, although reports of its actual effect are conflicting. We show that, in our system, GSK3β promotes anterograde mitochondrial transport. Finally, we investigated the influence of cAMP elevation upon mitochondrial motility, and found a striking increase in mitochondrial motility and retrograde movement. DISC1, NDE1, and GSK3β are implicated as risk factors for major mental illness. Our demonstration that they function together within mitochondrial trafficking complexes suggests that defective mitochondrial transport may be a contributory disease mechanism in some cases of psychiatric disorder. PMID:26815013

  12. Pig Brain Mitochondria as a Biological Model for Study of Mitochondrial Respiration.

    Science.gov (United States)

    Fišar, Z; Hroudová, J

    2016-01-01

    Oxidative phosphorylation is a key process of intracellular energy transfer by which mitochondria produce ATP. Isolated mitochondria serve as a biological model for understanding the mitochondrial respiration control, effects of various biologically active substances, and pathophysiology of mitochondrial diseases. The aim of our study was to evaluate pig brain mitochondria as a proper biological model for investigation of activity of the mitochondrial electron transport chain. Oxygen consumption rates of isolated pig brain mitochondria were measured using high-resolution respirometry. Mitochondrial respiration of crude mitochondrial fraction, mitochondria purified in sucrose gradient, and mitochondria purified in Percoll gradient were assayed as a function of storage time. Oxygen flux and various mitochondrial respiratory control ratios were not changed within two days of mitochondria storage on ice. Leak respiration was found higher and Complex I-linked respiration lower in purified mitochondria compared to the crude mitochondrial fraction. Damage to both outer and inner mitochondrial membrane caused by the isolation procedure was the greatest after purification in a sucrose gradient. We confirmed that pig brain mitochondria can serve as a biological model for investigation of mitochondrial respiration. The advantage of this biological model is the stability of respiratory parameters for more than 48 h and the possibility to isolate large amounts of mitochondria from specific brain areas without the need to kill laboratory animals. We suggest the use of high-resolution respirometry of pig brain mitochondria for research of the neuroprotective effects and/or mitochondrial toxicity of new medical drugs.

  13. Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins.

    Science.gov (United States)

    Birsa, Nicol; Norkett, Rosalind; Higgs, Nathalie; Lopez-Domenech, Guillermo; Kittler, Josef T

    2013-12-01

    Correct mitochondrial dynamics are essential to neuronal function. These dynamics include mitochondrial trafficking and quality-control systems that maintain a precisely distributed and healthy mitochondrial network, so that local energy demands or Ca2+-buffering requirements within the intricate architecture of the neuron can be met. Mitochondria make use of molecular machinery that couples these organelles to microtubule-based transport via kinesin and dynein motors, facilitating the required long-range movements. These motors in turn are associated with a variety of adaptor proteins allowing additional regulation of the complex dynamics demonstrated by these organelles. Over recent years, a number of new motor and adaptor proteins have been added to a growing list of components implicated in mitochondrial trafficking and distribution. Yet, there are major questions that remain to be addressed about the regulation of mitochondrial transport complexes. One of the core components of this machinery, the mitochondrial Rho GTPases Miro1 (mitochondrial Rho 1) and Miro2 have received special attention due to their Ca2+-sensing and GTPase abilities, marking Miro an exceptional candidate for co-ordinating mitochondrial dynamics and intracellular signalling pathways. In the present paper, we discuss the wealth of literature regarding Miro-mediated mitochondrial transport in neurons and recently highlighted involvement of Miro proteins in mitochondrial turnover, emerging as a key process affected in neurodegeneration. PMID:24256248

  14. Regulation of Mitochondrial Respiratory Chain Biogenesis by Estrogens/Estrogen Receptors and Physiological, Pathological and Pharmacological Implications

    OpenAIRE

    Chen, Jin-Qiang; Cammarata, Patrick R.; Baines, Christopher P.; Yager, James D.

    2009-01-01

    There has been increasing evidence pointing to the mitochondrial respiratory chain (MRC) as a novel and important target for the actions of 17β-estradiol(E2) and estrogen receptors (ER) in a number of cell types and tissues that have high demands for mitochondrial energy metabolism. This novel E2-mediated mitochondrial pathway involves the cooperation of both nuclear and mitochondrial ERα and ERβ and their co-activators on the coordinate regulation of both nuclear DNA- and mitochondrial DNA-e...

  15. Physical fitness and mitochondrial respiratory capacity in horse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Dominique-Marie Votion

    Full Text Available BACKGROUND: Within the animal kingdom, horses are among the most powerful aerobic athletic mammals. Determination of muscle respiratory capacity and control improves our knowledge of mitochondrial physiology in horses and high aerobic performance in general. METHODOLOGY/PRINCIPAL FINDINGS: We applied high-resolution respirometry and multiple substrate-uncoupler-inhibitor titration protocols to study mitochondrial physiology in small (1.0-2.5 mg permeabilized muscle fibres sampled from triceps brachii of healthy horses. Oxidative phosphorylation (OXPHOS capacity (pmol O(2 • s(-1 • mg(-1 wet weight with combined Complex I and II (CI+II substrate supply (malate+glutamate+succinate increased from 77 ± 18 in overweight horses to 103 ± 18, 122 ± 15, and 129 ± 12 in untrained, trained and competitive horses (N = 3, 8, 16, and 5, respectively. Similar to human muscle mitochondria, equine OXPHOS capacity was limited by the phosphorylation system to 0.85 ± 0.10 (N = 32 of electron transfer capacity, independent of fitness level. In 15 trained horses, OXPHOS capacity increased from 119 ± 12 to 134 ± 37 when pyruvate was included in the CI+II substrate cocktail. Relative to this maximum OXPHOS capacity, Complex I (CI-linked OXPHOS capacities were only 50% with glutamate+malate, 64% with pyruvate+malate, and 68% with pyruvate+malate+glutamate, and ~78% with CII-linked succinate+rotenone. OXPHOS capacity with glutamate+malate increased with fitness relative to CI+II-supported ETS capacity from a flux control ratio of 0.38 to 0.40, 0.41 and 0.46 in overweight to competitive horses, whereas the CII/CI+II substrate control ratio remained constant at 0.70. Therefore, the apparent deficit of the CI- over CII-linked pathway capacity was reduced with physical fitness. CONCLUSIONS/SIGNIFICANCE: The scope of mitochondrial density-dependent OXPHOS capacity and the density-independent (qualitative increase of CI-linked respiratory capacity with increased

  16. Impact of salinity on the aerobic metabolism of phosphate-accumulating organisms.

    Science.gov (United States)

    Welles, L; Lopez-Vazquez, C M; Hooijmans, C M; van Loosdrecht, M C M; Brdjanovic, D

    2015-04-01

    The use of saline water in urban areas for non-potable purposes to cope with fresh water scarcity, intrusion of saline water, and disposal of industrial saline wastewater into the sewerage lead to elevated salinity levels in wastewaters. Consequently, saline wastewater is generated, which needs to be treated before its discharge into surface water bodies. The objective of this research was to study the effects of salinity on the aerobic metabolism of phosphate-accumulating organisms (PAO), which belong to the microbial populations responsible for enhanced biological phosphorus removal (EBPR) in activated sludge systems. In this study, the short-term impact (hours) of salinity (as NaCl) was assessed on the aerobic metabolism of a PAO culture, enriched in a sequencing batch reactor (SBR). All aerobic PAO metabolic processes were drastically affected by elevated salinity concentrations. The aerobic maintenance energy requirement increased, when the salinity concentration rose up to a threshold concentration of 2 % salinity (on a W/V basis as NaCl), while above this concentration, the maintenance energy requirements seemed to decrease. All initial rates were affected by salinity, with the NH4- and PO4-uptake rates being the most sensitive. A salinity increase from 0 to 0.18 % caused a 25, 46, and 63 % inhibition of the O2, PO4, and NH4-uptake rates. The stoichiometric ratios of the aerobic conversions confirmed that growth was the process with the highest inhibition, followed by poly-P and glycogen formation. The study indicates that shock loads of 0.18 % salt, which corresponds to the use or intrusion of about 5 % seawater may severely affect the EBPR process already in wastewater treatment plants not exposed regularly to high salinity concentrations. PMID:25524698

  17. Data for mitochondrial proteomic alterations in the developing rat brain.

    Science.gov (United States)

    Villeneuve, Lance M; Stauch, Kelly L; Fox, Howard S

    2014-12-01

    Mitochondria are a critical organelle involved in many cellular processes, and due to the nature of the brain, neuronal cells are almost completely reliant on these organelles for energy generation. Due to the fact that biomedical research tends to investigate disease state pathogenesis, one area of mitochondrial research commonly overlooked is homeostatic responses to energy demands. Therefore, to elucidate mitochondrial alterations occurring during the developmentally important phase of E18 to P7 in the brain, we quantified the proteins in the mitochondrial proteome as well as proteins interacting with the mitochondria. We identified a large number of significantly altered proteins involved in a variety of pathways including glycolysis, mitochondrial trafficking, mitophagy, and the unfolded protein response. These results are important because we identified alterations thought to be homeostatic in nature occurring within mitochondria, and these results may be used to identify any abnormal deviations in the mitochondrial proteome occurring during this period of brain development. A more comprehensive analysis of this data may be obtained from the article "Proteomic analysis of mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands" in the Journal of Proteomics. PMID:26217684

  18. Dopamine Coupling to Mitochondrial Signaling: Implications for Transplantation.

    Science.gov (United States)

    Stefano, George B; Ramin, Rohina; Kream, Richard M

    2016-01-01

    The persistence of major medical disorders afflicting millions of humans worldwide involves a functional pathophysiological coupling of systemic pro-inflammatory processes and tissue hypoxia. Mechanistically, reciprocal triggering of multiple ischemic/hypoxic and pro-inflammatory events, if not corrected, will promote pathophysiological amplification leading to a deleterious cascade of bio-senescent cellular and molecular signaling pathways that converge to markedly impair mitochondrial energy production. Given the level of energy production and utilization that can vary in and between cells and regionally in the same type of cells found in the body, e.g., dopamine neurons, the metabolic energy regulator, the mitochondrion, assumes a high position in the potential to maintain normal health and develop abnormal activities, resulting in chronic pathologies. The intra-mitochondrial availability of molecular oxygen as the ultimate electron acceptor drives the evolutionarily fashioned chemiosmotic production of ATP as a high-efficiency biological proton pump process. The mechanistic evolutionary bases of diabetes have demonstrated the profound alteration of normative mitochondrial function, notably deregulated respiratory processes. This same phenomenon provides evidence of mitochondrial linkages to neurological disorders, such as Parkinson's disease. To date, and despite considerable research efforts, the practical realization of advanced mitochondrial targeted therapies has not been forthcoming. PMID:26790458

  19. A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy.

    Science.gov (United States)

    Jonckheere, An I; Hogeveen, Marije; Nijtmans, Leo; van den Brand, Mariel; Janssen, Antoon; Diepstra, Heleen; van den Brandt, Frans; van den Heuvel, Bert; Hol, Frans; Hofste, Tom; Kapusta, Livia; Dillmann, U; Shamdeen, M; Smeitink, J; Smeitink, J; Rodenburg, Richard

    2009-01-01

    To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder.Measurement of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme analysis in muscle and fibroblasts were performed. Relevant parts of the mitochondrial DNA were analysed by sequencing.A homoplasmic nonsense mutation m.8529G→A (p.Trp55X) was found in the mitochondrial ATP8 gene in the patient's fibroblasts and muscle tissue. Reduced complex V activity was measured in the patient's fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNAWe describe the first pathogenic mutation in the mitochondrial ATP8 gene, resulting in an improper assembly and reduced activity of the complex V holoenzyme. PMID:21686774

  20. Acute Aerobic Exercise and Plasma Levels of Orexin A, Insulin, Glucose, and Insulin Resistance in Males With Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Alizadeh

    2016-01-01

    Full Text Available Background The endocrine system disruptions are the main factors in metabolic disorders which are due to lifestyle changes, obesity, and aging. Insulin resistance is impaired glucose homeostasis in the presence of insulin and is related to many diseases such as hypertension, coronary artery disease, and type 2 diabetes Objectives This study aimed to investigate the effect of acute aerobic exercise on plasma levels of orexin A, insulin, glucose, and insulin resistance in males with type 2 diabetes. Patients and Methods Twenty subjects (mean age = 45.40 ± 5.42 years, mean weight = 80.91 ± 6.35 kg, body mass index = 25.41 ± 2.76 kg/m2 were randomly assigned into control and experimental groups, involving 10 people in each group. The exercise protocol consisted of one session of acute aerobic exercise on a treadmill at 60% maximal oxygen uptake and the same energy expenditure (300 kcal, which were determined by gas analyzers. Subjects were subjected to samplings before, immediately after, and 24 hours after the acute aerobic exercise. Results The analysis of findings in P ≤ 0.05 indicated that acute aerobic exercise caused a significant increase in plasma levels of orexin A and a significant decrease in plasma levels of glucose immediately after the aerobic activity, but insignificantly affected the plasma levels of insulin and insulin resistance. Conclusions It seems that in people with type 2 diabetes, acute aerobic exercise can decrease the plasma levels of glucose, possibly through increasing orexin A. In addition, negative energy balance is necessary to decrease the levels of insulin and insulin resistance during acute aerobic exercise.

  1. Mitochondrial Defects And Their Role In Development Of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Nanuli Kotrikadze

    2012-04-01

    Full Text Available Introduction and Objectives: One of the characteristic changes of tumor formation is accumulation of genetic disorders in mitochondrial and nuclear genome. Mitochondrial disorders, from its side, are responsible for failure of metabolism, apoptosis, cell growth, formation of reactive oxygen species, etc. Overprpoduction of reactive oxygen species (ROS significantly impacts the respiration chain enzymes and entirely the antioxidant system of mitochondria. Finally this may become a favorable condition for normal cells transformation.The purpose of the presented work was to study  the mitochondrial defects and to establish their role in prostate cancer development.Results: Experimental results demonstrate significant increase of the activity of mitochondrial succinate dehydrogenaze (complex II of the malignant epithelial cells of prostate, and slight changes in cytochrome oxydase (complex IV activity. Also significant activation of the antioxidant system (glutathione-dependant system of mitochondria in prostate malignant epithelial cells was revealed.Conclusion: The above mentioned mitochondrial changes (II and IV complexes of respiration chain, activity of the antioxidant system partially demonstrate the alterations in mitochondrial energy metabolism, which from its side, may indicate to resistance of prostate cancer cells and correspondingly to intensification of proliferation processes.

  2. The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity.

    Science.gov (United States)

    Love, Lorenzo K; LeBlanc, Paul J; Inglis, J Greig; Bradley, Nicolette S; Choptiany, Jon; Heigenhauser, George J F; Peters, Sandra J

    2011-08-01

    Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼ 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼ 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity). PMID:21596918

  3. Weed competitiveness and yielding ability of aerobic rice genotypes

    OpenAIRE

    Zhao, D.L.

    2006-01-01

    Keywords:    Broad-sense heritability; Crop vigour; Genetic correlation; Indirect selection index; Plant erectness; Rice germplasm; Seeding rate; Vegetative growth; Weed-suppressive ability.Aerobic rice, grown under aerobic soil conditions like maize or wheat, is an innovative way to cope with the growing demand for rice and the increasing water scarcity. Weeds are the most severe constraint to aerobic rice. The use of herbicides causes environmental pollution and induces the proliferation of...

  4. Perfection aerobic possibilities of athletes in sport dance.

    Directory of Open Access Journals (Sweden)

    Lee Bo

    2011-04-01

    Full Text Available The organized analysis to functions of the aerobic metabolism of the sport dancers. They are determined reduced components of the aerobic metabolism of partners (male and female. The motivated directivity of the training means and program for development component of the aerobic functions skilled athlete in sport dance. It is proved that loading that is used in training process by sport dances must have a character of cardiorespiratory system.

  5. The biological degradation as an energy option, determination of the effects of the aerobic phase on the subsequent production of biogas in a sanitary landfill; La degradacion biologica como una opcion energetica, determinacion de los efectos de la fase aerobia sobre la subsecuente produccion de biogas en un relleno sanitario

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar Juarez, Oscar [Asesoria de Servicios Ambientales del Bajio (ASSB), (Mexico)

    2010-07-01

    The present work deals with the energy evaluation of biological processes as energy source and is based on works concerning laboratory, pilot and field research. The objective of the research is to integrate the effect of the aerobic phase during the process of degradation of organic residues (basically the organic fraction of domestic residues), where the last aim is the biogas production. The usefulness of the results is reflected in the suitable estimation of the filling of a sanitary landfill considering the composition of the residues deposited and the effects that this management will have on the run-up time of the same and the velocity of biogas production. Finally, integrates a reflection on the intrinsic energy implications of the process and of the biogas yielding, which is evaluated as well as energy source. [Spanish] El presente trabajo trata sobre la valoracion energetica de procesos biologicos como fuente de energia y se basa en trabajos de investigacion a nivel de laboratorio, piloto y de campo. El objetivo de la investigacion es integrar el efecto de la fase aerobia durante el proceso de degradacion de residuos organicos (basicamente la fraccion organica de residuos domesticos), donde el fin ultimo es la produccion de biogas. La utilidad de los resultados se refleja en la estimacion adecuada del llenado de un relleno sanitario considerando la composicion de los residuos ahi depositados y los efectos que tendra esta gestion sobre el tiempo de estabilizacion de los mismos y la velocidad de produccion de biogas. Finalmente, se integra una reflexion sobre las implicaciones energeticas intrinsecas al proceso y del rendimiento de biogas, el cual a su vez es valorizado como fuente de energia.

  6. A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy.

    NARCIS (Netherlands)

    Jonckheere, A.I.; Hogeveen, M.; Nijtmans, L.G.J.; Brand, M.A.M. van den; Janssen, A.J.M.; Diepstra, J.H.S.; Brandt, FC van den; Heuvel, L.P.W.J. van den; Hol, F.A.; Hofste, T.G.; Kapusta, L.; Dillmann, U.; Shamdeen, M.G.; Smeitink, J.A.M.; Rodenburg, R.J.T.

    2008-01-01

    PURPOSE: To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder. METHODS: Measurement of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme

  7. ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones.

    Science.gov (United States)

    Masuda, Takamasa; Wada, Yasutaka; Kawamura, Satoru

    2016-03-01

    Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. During the mitochondrial growth, individual mitochondria have been considered to be enlarged independently of mitochondrial fusion. However, molecular basis for this enlarging process has been poorly understood. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. Here we show that ES1 is a novel mitochondria-enlarging factor contributing to form mega-mitochondria in cones. ES1 is specifically expressed in cones and localized to mitochondria including mega-mitochondria. Knockdown of ES1 markedly reduced the mitochondrial size in cones. In contrast, ectopic expression of ES1 in rods significantly increased both the size of individual mitochondria and the total mass of the mitochondrial cluster without changing the number of them. RNA-seq analysis showed that ERRα and its downstream mitochondrial genes were significantly up-regulated in the ES1-expressing rods, suggesting facilitation of mitochondrial enlargement via ERRα-dependent processes. Furthermore, higher energy state was detected in the ES1-expressing rods, indicating that the enlarged mitochondria by ES1 are capable of producing high energy. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria.

  8. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress.

    Science.gov (United States)

    Picard, Martin; McManus, Meagan J; Gray, Jason D; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K; Seifert, Erin L; McEwen, Bruce S; Wallace, Douglas C

    2015-12-01

    The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism's multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic-pituitary-adrenal axis, sympathetic adrenal-medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

  9. Divergent mitochondrial respiratory chains in phototrophic relatives of apicomplexan parasites

    KAUST Repository

    Flegontov, Pavel

    2015-02-06

    Four respiratory complexes and ATP-synthase represent central functional units in mitochondria. In some mitochondria and derived anaerobic organelles, a few or all of these respiratory complexes have been lost during evolution. We show that the respiratory chain of Chromera velia, a phototrophic relative of parasitic apicomplexans, lacks complexes I and III, making it a uniquely reduced aerobic mitochondrion. In Chromera, putative lactate:cytochrome c oxidoreductases are predicted to transfer electrons from lactate to cytochrome c, rendering complex III unnecessary. The mitochondrial genome of Chromera has the smallest known protein-coding capacity of all mitochondria, encoding just cox1 and cox3 on heterogeneous linear molecules. In contrast, another photosynthetic relative of apicomplexans, Vitrella brassicaformis, retains the same set of genes as apicomplexans and dinoflagellates (cox1, cox3, and cob). © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. The acylphloroglucinols hyperforin and myrtucommulone A cause mitochondrial dysfunctions in leukemic cells by direct interference with mitochondria.

    Science.gov (United States)

    Wiechmann, Katja; Müller, Hans; Fischer, Dagmar; Jauch, Johann; Werz, Oliver

    2015-11-01

    The acylphloroglucinols hyperforin (Hypf) and myrtucommulone A (MC A) induce death of cancer cells by triggering the intrinsic/mitochondrial pathway of apoptosis, accompanied by a loss of the mitochondrial membrane potential and release of cytochrome c. However, the upstream targets and mechanisms leading to these mitochondrial events in cancer cells remain elusive. Here we show that Hypf and MC A directly act on mitochondria derived from human leukemic HL-60 cells and thus, disrupt mitochondrial functions. In isolated mitochondria, Hypf and MC A efficiently impaired mitochondrial viability (EC50 = 0.2 and 0.9 µM, respectively), caused loss of the mitochondrial membrane potential (at 0.03 and 0.1 µM, respectively), and suppressed mitochondrial ATP synthesis (IC50 = 0.2 and 0.5 µM, respectively). Consequently, the compounds activated the adenosine monophosphate-activated protein kinase (AMPK) in HL-60 cells, a cellular energy sensor involved in apoptosis of cancer cells. Side by side comparison with the protonophore CCCP and the ATP synthase inhibitor oligomycin suggest that Hypf and MC A act as protonophores that primarily dissipate the mitochondrial membrane potential by direct interaction with the mitochondrial membrane. Together, Hypf and MC A abolish the mitochondrial proton motive force that on one hand impairs mitochondrial viability and on the other cause activation of AMPK due to lowered ATP levels which may further facilitate the intrinsic mitochondrial pathway of apoptosis.

  11. Research on aerobics classes influence on physical prepareduess of students.

    Directory of Open Access Journals (Sweden)

    Krasulia M. А.

    2011-04-01

    Full Text Available Physical skills of female students doing aerobics have been studied. 165 female students aged 17-18 divided into three groups of 55 each have taken part in the experiment. Groups have been trained according to different methods conventionally called 'power aerobics', 'dance aerobics' and 'jump aerobics'. Level of female students' physical skills has been determined by the results of seven tests in the beginning of an academic year and after six-months term. Mathematical treatment of the results has been carried out. The most preferable as to improving physical skills level method has been discovered to be the one aimed on power abilities development method.

  12. Aerobic capacity related to cardiac size in young children

    DEFF Research Database (Denmark)

    Dencker, M; Wollmer, P; Karlsson, M;

    2013-01-01

    Aerobic capacity, defined as peak oxygen uptake (VO2PEAK), is generally considered to be the best single marker for aerobic fitness. We assessed if VO2PEAK is related to different cardiac dimensions in healthy young children on a population base.......Aerobic capacity, defined as peak oxygen uptake (VO2PEAK), is generally considered to be the best single marker for aerobic fitness. We assessed if VO2PEAK is related to different cardiac dimensions in healthy young children on a population base....

  13. Effects of aerobic training on heart rate

    Directory of Open Access Journals (Sweden)

    Marcos B. Almeida

    2003-04-01

    Full Text Available Regular physical exercise is an important factor to reduce the indexes of cardiovascular and all causes morbimortality. However, there is, apparently, additional and independent benefits of the regular practice of physical exercise and the improvement of the level of aerobic condition. Heart rate (HR is mediated primarily by the direct activity of the autonomic nervous system (ANS, specifically through the sympathetic and parasympathetic branches activities over the sinus node autorhythmicity, with predominance of the vagal activity (parasympathetic at rest, that is progressively inhibited since the onset of the exercise. The HR behavior has been widely studied during different conditions and protocols associated to the exercise. A reduction of the cardiac vagal tone (parasympathetic function and consequently a diminished HR variability in rest, independently of the protocol of measurement used, is related to an autonomic dysfunction, chronic-degenerative diseases and increased mortality risk. Individuals with high levels of aerobic condition have a lower resting HR, along with a larger parasympathetic activity or smaller sympathetic activity, but it is not necessarily a direct consequence of the exercise training, as long as other inherent adaptations to the aerobic conditioning can influence the resting HR. The HR response in the onset of the exercise represents the integrity of the vagus nerve, and the HR recovery on the post-exercise transient also denotes important prognostic information; by the way, individuals that have a slow HR recovery in the first minute post-exercise have increased mortality risk. In conclusion, the physiological mechanisms modulating HR during or after an exercise program are not totally clear, and further studies are needed.

  14. Aerobic Biostabilization of Old MSW Landfills

    Directory of Open Access Journals (Sweden)

    M. C. Zanetti

    2008-01-01

    Full Text Available Many years after the end of the cultivation phase, landfills may generate intense odours, toxic and explosive gases and heavily-polluted leachate. A wide-spreading trend in the management of MSW landfills is represented by the forced aeration of wastes in order to achieve the stabilization, reducing the negative environmental impact of uncontrolled sites (old landfills which can be definitely considered as contaminated sites and the management costs of controlled and working facilities. One of the most interesting challenges is the in situ waste aerobic stabilization, obtained by insufflating air into the wastes. The aerobic metabolism is energetically convenient in comparison with the anaerobic one, it is characterized by a higher degradation rate and a temperature increase (like in the compost production. In order to obtain an aerobic biostabilization of waste in landfills, several air injection systems have been developed and applied in the last years, like Biopuster© or AEROflott® patented systems. The feasibility of the application of in situ biostabilization must be evaluated by means of different tests, in order to evaluate the main characteristics of the wastes. The main parameters to be evaluated are the biological stability and the air permeability of the wastes. In March 2006, the biological stability of the wastes located in the Trinitapoli Landfill, Italy, has been evaluated by the Politecnico di Torino. Black Index Test and Static Respirometric Index Test have been performed in the laboratories of the Politecnico. On the basis of the obtained results, the potential biogas production from the examined landfill was estimated together with the potential volume reduction.

  15. Sugarcane genes related to mitochondrial function

    Directory of Open Access Journals (Sweden)

    Fonseca Ghislaine V.

    2001-01-01

    Full Text Available Mitochondria function as metabolic powerhouses by generating energy through oxidative phosphorylation and have become the focus of renewed interest due to progress in understanding the subtleties of their biogenesis and the discovery of the important roles which these organelles play in senescence, cell death and the assembly of iron-sulfur (Fe/S centers. Using proteins from the yeast Saccharomyces cerevisiae, Homo sapiens and Arabidopsis thaliana we searched the sugarcane expressed sequence tag (SUCEST database for the presence of expressed sequence tags (ESTs with similarity to nuclear genes related to mitochondrial functions. Starting with 869 protein sequences, we searched for sugarcane EST counterparts to these proteins using the basic local alignment search tool TBLASTN similarity searching program run against 260,781 sugarcane ESTs contained in 81,223 clusters. We were able to recover 367 clusters likely to represent sugarcane orthologues of the corresponding genes from S. cerevisiae, H. sapiens and A. thaliana with E-value <= 10-10. Gene products belonging to all functional categories related to mitochondrial functions were found and this allowed us to produce an overview of the nuclear genes required for sugarcane mitochondrial biogenesis and function as well as providing a starting point for detailed analysis of sugarcane gene structure and physiology.

  16. Dancing the aerobics "Hearing loss choreography"

    OpenAIRE

    Beatriz M. Pinto; Carvalho, A.; Sérgio Oliveira

    2002-01-01

    This paper presents an overview of the health clubs acoustic problems when used for aerobics exercises classes (and similar) with loud noise levels in sound amplified music. A sample of five schools in Portugal was chosen for this survey. Noise levels in each room were measured and analyzed to calculate the standardized daily personal noise exposure levels (Leq8). Leq8 values up to 96 dB(A) were found in this type of room inducing a health risk for its occupants. This type of gymnasium is usu...

  17. [Heterotrophic Nitrification and Aerobic Denitrification of the Hypothermia Aerobic Denitrification Bacterium: Arthrobacter arilaitensis].

    Science.gov (United States)

    He, Teng-xia; Ni, Jiu-pai; Li, Zhen-lun; Sun, Quan; Ye Qing; Xu, Yi

    2016-03-15

    High concentrations of ammonium, nitrate and nitrite nitrogen were employed to clarify the abilities of heterotrophic nitrification and aerobic denitrification of Arthrobacter arilaitensis strain Y-10. Meanwhile, by means of inoculating the strain suspension into the mixed ammonium and nitrate, ammonium and nitrite nitrogen simulated wastewater, we studied the simultaneous nitrification and denitrification ability of Arthrobacter arilaitensis strain Y-10. In addition, cell optical density was assayed in each nitrogen removal process to analyze the relationship of cell growth and nitrogen removal efficiency. The results showed that the hypothermia denitrification strain Arthrobacter arilaitensis Y-10 exhibited high nitrogen removal efficiency during heterotrophic nitrification and aerobic denitrification. The ammonium, nitrate and nitrite removal rates were 65.0%, 100% and 61.2% respectively when strain Y-10 was cultivated for 4 d at 15°C with initial ammonium, nitrate and nitrite nitrogen concentrations of 208.43 mg · L⁻¹, 201.16 mg · L⁻¹ and 194.33 mg · L⁻¹ and initial pH of 7.2. Nitrite nitrogen could only be accumulated in the medium containing nitrate nitrogen during heterotrophic nitrification and aerobic denitrification process. Additionally, the ammonium nitrogen was mainly removed in the inorganic nitrogen mixed synthetic wastewater. In short, Arthrobacter arilaitensis Y-10 could conduct nitrification and denitrification effectively under aerobic condition and the ammonium nitrogen removal rate was more than 80.0% in the inorganic nitrogen mixed synthetic wastewater. PMID:27337904

  18. Mitochondrial helicases and mitochondrial genome maintenance

    DEFF Research Database (Denmark)

    de Souza-Pinto, Nadja C; Aamann, Maria Diget; Kulikowicz, Tomasz;

    2010-01-01

    Helicases are essential enzymes that utilize the energy of nucleotide hydrolysis to drive unwinding of nucleic acid duplexes. Helicases play roles in all aspects of DNA metabolism including DNA repair, DNA replication and transcription. The subcellular locations and functions of several helicases...

  19. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  20. Respiratory active mitochondrial supercomplexes.

    Science.gov (United States)

    Acín-Pérez, Rebeca; Fernández-Silva, Patricio; Peleato, Maria Luisa; Pérez-Martos, Acisclo; Enriquez, Jose Antonio

    2008-11-21

    The structural organization of the mitochondrial respiratory complexes as four big independently moving entities connected by the mobile carriers CoQ and cytochrome c has been challenged recently. Blue native gel electrophoresis reveals the presence of high-molecular-weight bands containing several respiratory complexes and suggesting an in vivo assembly status of these structures (respirasomes). However, no functional evidence of the activity of supercomplexes as true respirasomes has been provided yet. We have observed that (1) supercomplexes are not formed when one of their component complexes is absent; (2) there is a temporal gap between the formation of the individual complexes and that of the supercomplexes; (3) some putative respirasomes contain CoQ and cytochrome c; (4) isolated respirasomes can transfer electrons from NADH to O(2), that is, they respire. Therefore, we have demonstrated the existence of a functional respirasome and propose a structural organization model that accommodates these findings.

  1. Aerobic degradation of sulfanilic acid using activated sludge.

    Science.gov (United States)

    Chen, Gang; Cheng, Ka Yu; Ginige, Maneesha P; Kaksonen, Anna H

    2012-01-01

    This paper evaluates the aerobic degradation of sulfanilic acid (SA) by an acclimatized activated sludge. The sludge was enriched for over three months with SA (>500 mg/L) as the sole carbon and energy source and dissolved oxygen (DO, >5mg/L) as the primary electron acceptor. Effects of aeration rate (0-1.74 L/min), DO concentration (0-7 mg/L) and initial SA concentration (104-1085 mg/L) on SA biodegradation were quantified. A modified Haldane substrate inhibition model was used to obtain kinetic parameters of SA biodegradation and oxygen uptake rate (OUR). Positive linear correlations were obtained between OUR and SA degradation rate (R(2)≥ 0.91). Over time, the culture consumed more oxygen per SA degraded, signifying a gradual improvement in SA mineralization (mass ratio of O(2): SA at day 30, 60 and 120 were 0.44, 0.51 and 0.78, respectively). The concomitant release of near stoichiometric quantity of sulphate (3.2 mmol SO(4)(2-) released from 3.3 mmol SA) and the high chemical oxygen demand (COD) removal efficacy (97.1%) indicated that the enriched microbial consortia could drive the overall SA oxidation close to a complete mineralization. In contrast to other pure-culture systems, the ammonium released from the SA oxidation was predominately converted into nitrate, revealing the presence of ammonium-oxidizing bacteria (AOB) in the mixed culture. No apparent inhibitory effect of SA on the nitrification was noted. This work also indicates that aerobic SA biodegradation could be monitored by real-time DO measurement.

  2. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Møller, Ian Max; Salvato, Fernanda; Havelund, Jesper;

    We are testing the hypothesis that oxidized peptides are released from stressed mitochondria and contribute to retrograde signalling (Møller IM & Sweetlove LJ 2010 Trends Plant Sci 15, 370-374). However, there is a large gap between the number of experimentally verified mitochondrial proteins (~450......) and in silico-predicted mitochondrial proteins (2000-3000). Thus, before starting to look for oxidized peptides, we wanted to expand the current compendium of plant mitochondrial proteins while obtaining what could be termed the "baseline proteome" from our model organelle, the potato tuber mitochondrion. Its...

  3. Efficient production and secretion of pyruvate from Halomonas sp. KM-1 under aerobic conditions

    OpenAIRE

    Kawata, Yoshikazu; Nishimura, Taku; MATSUSHITA, ISAO; Tsubota, Jun

    2016-01-01

    The alkaliphilic, halophilic bacterium Halomonas sp. KM-1 can utilize both hexose and pentose sugars for the intracellular storage of bioplastic poly-(R)-3-hydroxybutyric acid (PHB) under aerobic conditions. In this study, we investigated the effects of the sodium nitrate concentration on PHB accumulation in the KM-1 strain. Unexpectedly, we observed the secretion of pyruvate, a central intermediate in carbon- and energy-metabolism processes in all organisms; therefore, pyruvate is widely use...

  4. “A Vegetarian vs. Conventional Hypocaloric Diet: The Effect on Physical Fitness in Response to Aerobic Exercise in Patients with Type 2 Diabetes.” A Parallel Randomized Study

    Directory of Open Access Journals (Sweden)

    Jiri Veleba

    2016-10-01

    Full Text Available It has been shown that it is possible to modify macronutrient oxidation, physical fitness and resting energy expenditure (REE by changes in diet composition. Furthermore, mitochondrial oxidation can be significantly increased by a diet with a low glycemic index. The purpose of our trial was to compare the effects of a vegetarian (V and conventional diet (C with the same caloric restriction (−500 kcal/day on physical fitness and REE after 12 weeks of diet plus aerobic exercise in 74 patients with type 2 diabetes (T2D. An open, parallel, randomized study design was used. All meals were provided for the whole study duration. An individualized exercise program was prescribed to the participants and was conducted under supervision. Physical fitness was measured by spiroergometry and indirect calorimetry was performed at the start and after 12 weeks Repeated-measures ANOVA (Analysis of variance models with between-subject (group and within-subject (time factors and interactions were used for evaluation of the relationships between continuous variables and factors. Maximal oxygen consumption (VO2max increased by 12% in vegetarian group (V (F = 13.1, p < 0.001, partial η2 = 0.171, whereas no significant change was observed in C (F = 0.7, p = 0.667; group × time F = 9.3, p = 0.004, partial η2 = 0.209. Maximal performance (Watt max increased by 21% in V (F = 8.3, p < 0.001, partial η2 = 0.192, whereas it did not change in C (F = 1.0, p = 0.334; group × time F = 4.2, p = 0.048, partial η2 = 0.116. Our results indicate that V leads more effectively to improvement in physical fitness than C after aerobic exercise program.

  5. Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

    Institute of Scientific and Technical Information of China (English)

    Minjong; Lee; Jung-Hwan; Yoon

    2015-01-01

    Aerobic glycolysis, i.e., the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e., the "reverse Warburg effect". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.

  6. Characterization and aerobic biodegradation of selected monoterpenes

    Energy Technology Data Exchange (ETDEWEB)

    Misra, G.; Pavlostathis, S.G.; Li, J.; Purdue, E.M. [Georgia Institute of Technology, Atlanta, GA (United States)

    1996-12-31

    Monoterpenes are biogenic chemicals and occur in abundance in nature. Large-scale industrial use of these chemicals has recently been initiated in an attempt to replace halogenated solvents and chlorofluorocarbons which have been implicated in the stratospheric depletion of ozone. This study examined four hydrocarbon monoterpenes (d-limonene, {alpha}-pinene, {gamma}-terpinene, and terpinolene) and four alcohols (arbanol, linalool, plinol, and {alpha}-terpineol). Water solubility, vapor pressure, and octanol/water partition coefficients were estimated. Aerobic biodegradability tests were conducted in batch reactors by utilizing forest soil extract and enriched cultures as inoculum. The hydrophobic nature and high volatility of the hydrocarbons restricted the investigation to relatively low aqueous concentrations. Each monoterpene was analyzed with a gas chromatograph equipped with a flame ionization detector after extraction from the aqueous phase with isooctane. Terpene mineralization was tested by monitoring liquid-phase carbon, CO{sub 2} production and biomass growth. All four hydrocarbons and two alcohols readily degraded under aerobic conditions. Plinol resisted degradation in assays using inocula from diverse sources, while arbanol degraded very slowly. The intrinsic biokinetics coefficients for the degradation of d-limonene and {alpha}-terpineol were estimated by using cultures enriched with the respective monoterpenes. Monoterpene biodegradation followed Monod kinetics.

  7. Aerobic Thermophilic Composting of Municipal Solid Waste

    Directory of Open Access Journals (Sweden)

    D V Wadkar

    2013-03-01

    Full Text Available Composting is a natural process that turns organic material into a dark rich substance called compost. Aerobic Composting is the creation of compost that depends on bacteria that thrive in an oxygen rich environment. Aerobic bacteria manage the chemical process by converting the inputs (i.e. air, water and carbon and nitrogen rich materials into heat, carbon dioxide and ammonium. The ammonium is further converted by bacteria into plant nourishing nitrites and nitrates through the process of nitrification. Thermophilic Composting is breaking down biological waste with thermophilic (heat loving bacteria. A cylindrical reactor was made. Organic wasteincluded dry vegetable waste collected from MSW ramp, Koregaon park, Pune. The characteristics of compost like pH, moisture content, temperature, C/N ratio and volume reduction were studied for the period of maturation (42days. It can be concluded that the values are within the desired limits and compost is suitable for ornamental plants. The setup of reactor is affordable and thus the compost obtained is effective and economical.

  8. Mitochondrial Stress: A Bridge between Mitochondrial Dysfunction and Metabolic Diseases?

    OpenAIRE

    Hu, Fang; Liu, Feng

    2011-01-01

    Under pathophysiological conditions such as obesity, excessive oxidation of nutrients may induce mitochondrial stress, leading to mitochondrial unfolded protein response (UPRmt) and initiation of a retrograde stress signaling pathway. Defects in the UPRmt and the retrograde signaling pathways may disrupt the integrity and homeostasis of the mitochondria, resulting endoplasmic reticulum stress and insulin resistance. Improving the capacity of mitochondria to reduce stress may be an effective a...

  9. Miro sculpts mitochondrial dynamics in neuronal health and disease.

    Science.gov (United States)

    Devine, Michael J; Birsa, Nicol; Kittler, Josef T

    2016-06-01

    Neurons are highly polarised cells with an elaborate and diverse cytoarchitecture. But this complex architecture presents a major problem: how to appropriately distribute metabolic resources where they are most needed within the cell. The solution comes in the form of mitochondria: highly dynamic organelles subject to a repertoire of trafficking, fission/fusion and quality control systems which work in concert to orchestrate a precisely distributed and healthy mitochondrial network. Mitochondria are critical for maintaining local energy supply and buffering Ca(2+) flux within neurons, and are increasingly recognised as being essential for healthy neuronal function. Mitochondrial movements are facilitated by their coupling to microtubule-based transport via kinesin and dynein motors. Adaptor proteins are required for this coupling and the mitochondrial Rho GTPases Miro1 and Miro2 are core components of this machinery. Both Miros have Ca(2+)-sensing and GTPase domains, and are therefore ideally suited to coordinating mitochondrial dynamics with intracellular signalling pathways and local energy turnover. In this review, we focus on Miro's role in mediating mitochondrial transport in neurons, and the relevance of these mechanisms to neuronal health and disease. PMID:26707701

  10. Effect Of Single And Short-Term Aerobics On Selected Mental State Parametres In Adult Females

    Directory of Open Access Journals (Sweden)

    Kyselovičová Oľga

    2015-11-01

    Full Text Available The aim of the study was to determine the degree of the influence of aerobic program on mental state of the trainees after a single and short-term application. We tried to find out the positive effects of an aerobics on the selected parameters of mental state of women that performed aerobics recreationally. Twenty-two healthy women (age 35 ± 5 years were involved in the specific aerobic program with mini trampolines (jumping over the period of 5 weeks. To measure the psychological parameters a modified questionnaire of type X-STAI was distributed before and after the single work out at the beginning of the study and after the 5 weeks period. Chi-quadrat analysis was used to evaluate the data. The greatest and statistically the most significant differences were recorded in the parameters ´enthusiastic´, ´boosted by energy´ and ´relaxed´, in comparison with the emotions at the beginning and at the end of the lesson in initial measuring. Comparison of changes after the 5 weeks period at the beginning and at the end of the lesson shows statistical significance in all parameters, except ´tired´. No statistical changes occurred at either the beginning or the end of the lesson comparing initial and final phases. Based on the results, we can conclude that specialized aerobic training provokes immediate changes in psychological state of the trainees via increase of their positive and decrease of negative emotions right after the lesson and when compared to its beginning. This leads to a better mental stability and a greater resistance to the influences of outer environment on mental state.

  11. Anthropometry, somatotypes, and aerobic power in ballet, contemporary dance, and dancesport.

    Science.gov (United States)

    Liiv, Helena; Wyon, Matthew A; Jürimäe, Toivo; Saar, Meeli; Mäestu, Jarek; Jürimäe, Jaak

    2013-12-01

    This study compared anthropometric variables, somatotypes, and aerobic capacity between three groups of dancers: classical ballet dancers (M 33, F 56), contemporary dancers (M 28, F 109), and dancesport dancers (M 30, F 30). The assumption was that different functional requirements should produce differences in the anthropometric and aerobic capacity variables among the three groups. Anthropometric data for body mass index (BMI) and somatotypes were measured. Body fat percentage was measured by dual-energy x-ray absorptiometry. Maximal oxygen consumption and aerobic power were measured during an incremental treadmill test until exhaustion. Dancesport athletes were taller compared with same gender contemporary dancers (p<0.05). Female ballet dancers had a lower body mass and BMI compared with their contemporary dance and dancesport equivalents (p<0.001). There was significant difference between dance styles in endomorphy (F2,221 = 8.773, p<0.001) and mesomorphy (F2,221 = 21.458, p<0.001) scores. Dancesport dancers had significantly greater VO2max values (p<0.01). It was concluded that female contemporary dancers are generally more muscular than their ballet counterparts, while dancesport dancers are taller and heavier, less muscular, with slightly greater adioposity compared to the classical ballet dancers. Ballet dancers had the lowest body fat percentage, weight, and BMI values. Dancesport dancers had greater aerobic capacity than the ballet dancers. Based on this study, we conclude that dancers in these three styles differ in some aspects of anthropometric variables, somatotypes, and aerobic capacity, but we cannot say is it because of the training or selection or both. PMID:24337032

  12. 线粒体功能障碍与心血管疾病%Roles of mitochondrial dysfunction in cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    熊燕; 张梅; 陈菲; 方伟进

    2013-01-01

    Mitochondria are important organelles of energy generation in eukaryocytes and play a pivotal role in cell calcium homeostasis, signal transduction and apoptotic regulation. The possible causes leading to mitochondrial dysfunction include oxidative stress, Ca + disorder, reduction of mitochondrial biosynthesis and mitochondrial DNA mutations, all of which are also closely related to the development of cardiovascular diseases. Understanding the mitochondrial dysfunction and its important role in cardiovascular diseases are very significant for elucidating the mechanisms of cardiovascular diseases.

  13. Aerobic effluent treatment with lower electric power consumption. Survey of results from questionnaire sent out to Swedish pulp and paper mills with biological effluent treatment plants; Aerob rening med laegre elfoerbrukning. Sammanstaellning av enkaetsvar fraan svenska skogsindustrier med biologisk rening

    Energy Technology Data Exchange (ETDEWEB)

    Sivard, Aasa; Simon, Olle

    2010-12-15

    A survey of the energy situation at 23 Swedish pulp and paper mills with aerobic effluent treatment plants has been performed. The electricity consumption for aeration equipment is about 80 % of the total electricity consumption. Proposed measures to increase energy efficiency are regular measurements of energy consumption, better control of the oxygen level in some mills and evaluation of measures to use the heat in process effluent before and after biological treatment

  14. Advances in Researches on Relations between Cold and Hot Properties of TCM and Mitochondrial Energy Metabolism%中药寒热药性与线粒体能量代谢关系研究

    Institute of Scientific and Technical Information of China (English)

    王艳艳; 孙雪; 裴晓蕾; 王秋红; 杨炳友; 匡海学

    2013-01-01

    中药具有寒,热之性,寒热药性是从药物的作用性质上对药物多种医疗作用的高度概括,是中药药性理论的核心内容.总结和反思寒热药性研究的前期成果发现,中医的寒证、热证与机体能量代谢的关系密切,寒热中药可能通过影响能量代谢的某些环节,实现对寒热证的调节.线粒体是细胞氧化供能的重要部位,线粒体中的关键酶、解偶联蛋白以及三羧酸循环节点代谢产物等在调控能量代谢方面发挥重要作用.基于线粒体能量代谢的中药寒热药性研究为揭示药性的本质研究提供了一个新的思路.%Traditional Chinese medicine (TCM) has the nature of cold and hot.Cold and hot properties are highly summarized that are from the nature of drug on a wide range of medical role,which is the core content of the theory of Chinese medicine properties.Summary and reflection of cold and hot properties that are from preliminary results show that it is closely related to the body's energy metabolism.Chills and fever Chinese medicine may affect some links of energy metabolism,achieve the regulation of symptoms caused by cold and hot factors.Mitochondria is the essential part of cellular oxidative and energy supply,key enzyme,uncoupling protein,and citric acid cycle node metabolites in mitochondria play an important role in the regulation of energy metabolism.Study of cold and hot properties based on mitochondrial energy metabolism provides a new way of thinking for revealing the herbal essence.

  15. Mitochondrial Dynamics Tracking with Two-Photon Phosphorescent Terpyridyl Iridium(III) Complexes

    Science.gov (United States)

    Huang, Huaiyi; Zhang, Pingyu; Qiu, Kangqiang; Huang, Juanjuan; Chen, Yu; Ji, Liangnian; Chao, Hui

    2016-02-01

    Mitochondrial dynamics, including fission and fusion, control the morphology and function of mitochondria, and disruption of mitochondrial dynamics leads to Parkinson’s disease, Alzheimer’s disease, metabolic diseases, and cancers. Currently, many types of commercial mitochondria probes are available, but high excitation energy and low photo-stability render them unsuitable for tracking mitochondrial dynamics in living cells. Therefore, mitochondrial targeting agents that exhibit superior anti-photo-bleaching ability, deep tissue penetration and intrinsically high three-dimensional resolutions are urgently needed. Two-photon-excited compounds that use low-energy near-infrared excitation lasers have emerged as non-invasive tools for cell imaging. In this work, terpyridyl cyclometalated Ir(III) complexes (Ir1-Ir3) are demonstrated as one- and two-photon phosphorescent probes for real-time imaging and tracking of mitochondrial morphology changes in living cells.

  16. Acetic acid treatment in S. cerevisiae creates significant energy deficiency and nutrient starvation that is dependent on the activity of the mitochondrial transcriptional complex Hap2-3-4-5.

    Science.gov (United States)

    Kitanovic, Ana; Bonowski, Felix; Heigwer, Florian; Ruoff, Peter; Kitanovic, Igor; Ungewiss, Christin; Wölfl, Stefan

    2012-01-01

    Metabolic pathways play an indispensable role in supplying cellular systems with energy and molecular building blocks for growth, maintenance and repair and are tightly linked with lifespan and systems stability of cells. For optimal growth and survival cells rapidly adopt to environmental changes. Accumulation of acetic acid in stationary phase budding yeast cultures is considered to be a primary mechanism of chronological aging and induction of apoptosis in yeast, which has prompted us to investigate the dependence of acetic acid toxicity on extracellular conditions in a systematic manner. Using an automated computer controlled assay system, we investigated and model the dynamic interconnection of biomass yield- and growth rate-dependence on extracellular glucose concentration, pH conditions and acetic acid concentration. Our results show that toxic concentrations of acetic acid inhibit glucose consumption and reduce ethanol production. In absence of carbohydrates uptake, cells initiate synthesis of storage carbohydrates, trehalose and glycogen, and upregulate gluconeogenesis. Accumulation of trehalose and glycogen, and induction of gluconeogenesis depends on mitochondrial activity, investigated by depletion of the Hap2-3-4-5 complex. Analyzing the activity of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK), and glucose-6-phosphate dehydrogenase (G6PDH) we found that while high acetic acid concentration increased their activity, lower acetic acids concentrations significantly inhibited these enzymes. With this study we determined growth and functional adjustment of metabolism to acetic acid accumulation in a complex range of extracellular conditions. Our results show that substantial acidification of the intracellular environment, resulting from accumulation of dissociated acetic acid in the cytosol, is required for acetic acid toxicity, which creates a state of energy deficiency and nutrient starvation.

  17. Acetic acid treatment in S.cerevisiae creates significant energy deficiency and nutrient starvation that is dependent on the activity of mitochondrial transcriptional complex Hap2-3-4-5.

    Directory of Open Access Journals (Sweden)

    Ana eKitanovic

    2012-09-01

    Full Text Available Metabolic pathways play an indispensable role in supplying cellular systems with energy and molecular building blocks for growth, maintenance and repair and are tightly linked with lifespan and systems stability of cells. For optimal growth and survival cells rapidly adopt to environmental changes. Accumulation of acetic acid in stationary phase budding yeast cultures is considered to be a primary mechanism of chronological aging and induction of apoptosis in yeast, which has prompted us to investigate the dependence of acetic acid toxicity on extracellular conditions in a systematic manner.Using an automated computer controlled assay system, we investigated and model the dynamic interconnection of biomass yield- and growth rate-dependence on extracellular glucose concentration, pH conditions and acetic acid concentration. Our results show that toxic concentrations of acetic acid inhibit glucose consumption and reduce ethanol production. In absence of carbohydrates uptake, cells initiate synthesis of storage carbohydrates, trehalose and glycogen, and upregulate gluconeogenesis. Accumulation of trehalose and glycogen, and induction of gluconeogenesis depends on mitochondrial activity, investigated by depletion of the Hap2-3-4-5 complex. Analyzing the activity of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, pyruvate kinase (PYK and glucose-6-phosphate dehydrogenase (G6PDH we found that while high acetic acid concentration increased their activity, lower acetic acids concentrations significantly inhibited these enzymes. With this study we determined growth and functional adjustment of metabolism to acetic acid accumulation in a complex range of extracellular conditions. Our results show that substantial acidification of the intracellular environment, resulting from accumulation of dissociated acetic acid in the cytosol, is required for acetic acid toxicity, which creates a state of energy deficiency and nutrient starvation.

  18. Differential production of slime under aerobic and anaerobic conditions.

    OpenAIRE

    Barker, L P; Simpson, W A; Christensen, G D

    1990-01-01

    A series of 37 clinical isolates of coagulase-negative staphylococci previously identified as negative for slime production by the tube test were reexamined by the tissue culture plate test under aerobic and anaerobic conditions. None of the strains produced slime under anaerobic conditions; however, five strains (13%) produced slime under aerobic conditions.

  19. Longitudinal Predictors of Aerobic Performance in Adolescent Soccer Players

    NARCIS (Netherlands)

    Valente-dos-Santos, Joao; Coelho-e-Silva, Manuel J.; Duarte, Joao; Figueiredo, Antonio J.; Liparotti, Joao R.; Sherar, Lauren B.; Elferink-Gemser, Marije T.; Malina, Robert M.

    2012-01-01

    Background. The importance of aerobic performance in youth soccer is well established. The aim of the present study was to evaluate the contributions of chronological age (CA), skeletal age (SA), body size, and training to the longitudinal development of aerobic performance in youth male soccer play

  20. Aerobic Fitness Thresholds Associated with Fifth Grade Academic Achievement

    Science.gov (United States)

    Wittberg, Richard; Cottrell, Lesley A.; Davis, Catherine L.; Northrup, Karen L.

    2010-01-01

    Background: Whereas effects of physical fitness and physical activity on cognitive function have been documented, little is known about how they are related. Purpose: This study assessed student aerobic fitness measured by FITNESSGRAM Mile times and/or Pacer circuits and whether the nature of the association between aerobic fitness and…

  1. Water Aerobics as a Form of Health Activities

    OpenAIRE

    Anna S. Batrak; Antonina V. Polyakova

    2013-01-01

    The offered literature review considers water aerobics as a form of health activities. Water aerobics is wide spread and popular, especially among women, because it is also the form of adaptive and health activities. It enlarges general physiological effect of physical exercises on the human body. Regular exercises improve physical fitness and physical development, health, mood, sleep, intensify activities and working efficiency.

  2. Aerobic Digestion. Student Manual. Biological Treatment Process Control.

    Science.gov (United States)

    Klopping, Paul H.

    This manual contains the textual material for a single-lesson unit on aerobic sludge digestion. Topic areas addressed include: (1) theory of aerobic digestion; (2) system components; (3) performance factors; (4) indicators of stable operation; and (5) operational problems and their solutions. A list of objectives, glossary of key terms, and…

  3. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.

    Science.gov (United States)

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-Sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-Quan; Hüttemann, Maik; Grossman, Lawrence I

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  4. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy

    Science.gov (United States)

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P.; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-quan; Hüttemann, Maik; Grossman, Lawrence I.

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  5. Genetic counseling in mitochondrial disease.

    Science.gov (United States)

    Vento, Jodie M; Pappa, Belen

    2013-04-01

    Mitochondrial diseases are a genetically and clinically diverse group of disorders that arise as a result of dysfunction of the mitochondria. Mitochondrial disorders can be caused by alterations in nuclear DNA and/or mitochondrial DNA. Although some mitochondrial syndromes have been described clearly in the literature many others present as challenging clinical cases with multisystemic involvement at variable ages of onset. Given the clinical variability and genetic heterogeneity of these conditions, patients and their families often experience a lengthy and complicated diagnostic process. The diagnostic journey may be characterized by heightened levels of uncertainty due to the delayed diagnosis and the absence of a clear prognosis, among other factors. Uncertainty surrounding issues of family planning and genetic testing may also affect the patient. The role of the genetic counselor is particularly important to help explain these complexities and support the patient and family's ability to achieve effective coping strategies in dealing with increased levels of uncertainty.

  6. Bioenergetic roles of mitochondrial fusion.

    Science.gov (United States)

    Silva Ramos, Eduardo; Larsson, Nils-Göran; Mourier, Arnaud

    2016-08-01

    Mitochondria are bioenergetic hotspots, producing the bulk of ATP by the oxidative phosphorylation process. Mitochondria are also structurally dynamic and undergo coordinated fusion and fission to maintain their function. Recent studies of the mitochondrial fusion machinery have provided new evidence in detailing their role in mitochondrial metabolism. Remarkably, mitofusin 2, in addition to its role in fusion, is important for maintaining coenzyme Q levels and may be an integral player in the mevalonate synthesis pathway. Here, we review the bioenergetic roles of mitochondrial dynamics and emphasize the importance of the in vitro growth conditions when evaluating mitochondrial respiration. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016,' edited by Prof. Paolo Bernardi. PMID:27060252

  7. Impact of intermittent aerations on leachate quality and greenhouse gas reduction in the aerobic-anaerobic landfill method.

    Science.gov (United States)

    Nag, Mitali; Shimaoka, Takayuki; Komiya, Teppei

    2016-09-01

    The aerobic-anaerobic landfill method (AALM) is a novel approach in solid waste management that could shorten the landfill post-closure period and minimize the environmental loads. In this study, the aerobic-anaerobic landfill method was evaluated by using intermittent aeration. In addition, the nitrification-denitrification process was assessed as a means of reducing the emission of greenhouse gases (GHGs) and improving the leachate quality during the degradation of the organic solid waste. The leachate quality and the gas composition in each of the reactors were measured during the experimental period (408days). The aeration process entailed the injection of air into plexiglass cylinders (200cm height×10 cm diameter), filled with fresh organic solid waste collected from a composting plant. Different aeration routines were applied, namely, continuous aeration (aerobic reactor A), aeration for three days/week (aerobic-anaerobic reactor B), aeration for 6h/day (aerobic-anaerobic reactor C), and no aeration (non-aerated reactor D). It was found that aerobic reactor A produced the best results in terms of reduction of GHGs and improvement of the leachate quality. The aerobic-anaerobic reactor C was found to be more effective than reactor B in respect of both the emission of GHGs and the leachate quality; moreover, compared with aerobic reactor A, energy costs were reduced by operating this reactor. The transition period phenomenon was investigated during an intensive seven-day experiment conducted on the discharged leachate obtained from aerobic-anaerobic reactors B and C. The experiment concerned the differences in the composition of the gas during the aeration and the non-aeration periods. It was found that the transition period between the aeration and non-aeration cycles, which followed the simultaneous nitrification-denitrification had a considerable effect on the leachate quality of both the reactors. The results indicated that AALM has the potential to reduce

  8. Impact of intermittent aerations on leachate quality and greenhouse gas reduction in the aerobic-anaerobic landfill method.

    Science.gov (United States)

    Nag, Mitali; Shimaoka, Takayuki; Komiya, Teppei

    2016-09-01

    The aerobic-anaerobic landfill method (AALM) is a novel approach in solid waste management that could shorten the landfill post-closure period and minimize the environmental loads. In this study, the aerobic-anaerobic landfill method was evaluated by using intermittent aeration. In addition, the nitrification-denitrification process was assessed as a means of reducing the emission of greenhouse gases (GHGs) and improving the leachate quality during the degradation of the organic solid waste. The leachate quality and the gas composition in each of the reactors were measured during the experimental period (408days). The aeration process entailed the injection of air into plexiglass cylinders (200cm height×10 cm diameter), filled with fresh organic solid waste collected from a composting plant. Different aeration routines were applied, namely, continuous aeration (aerobic reactor A), aeration for three days/week (aerobic-anaerobic reactor B), aeration for 6h/day (aerobic-anaerobic reactor C), and no aeration (non-aerated reactor D). It was found that aerobic reactor A produced the best results in terms of reduction of GHGs and improvement of the leachate quality. The aerobic-anaerobic reactor C was found to be more effective than reactor B in respect of both the emission of GHGs and the leachate quality; moreover, compared with aerobic reactor A, energy costs were reduced by operating this reactor. The transition period phenomenon was investigated during an intensive seven-day experiment conducted on the discharged leachate obtained from aerobic-anaerobic reactors B and C. The experiment concerned the differences in the composition of the gas during the aeration and the non-aeration periods. It was found that the transition period between the aeration and non-aeration cycles, which followed the simultaneous nitrification-denitrification had a considerable effect on the leachate quality of both the reactors. The results indicated that AALM has the potential to reduce

  9. The mitochondrial Ca2+ uniporter: regulation by auxiliary subunits and signal transduction pathways.

    Science.gov (United States)

    Jhun, Bong Sook; Mishra, Jyotsna; Monaco, Sarah; Fu, Deming; Jiang, Wenmin; Sheu, Shey-Shing; O-Uchi, Jin

    2016-07-01

    Mitochondrial Ca(2+) homeostasis, the Ca(2+) influx-efflux balance, is responsible for the control of numerous cellular functions, including energy metabolism, generation of reactive oxygen species, spatiotemporal dynamics of Ca(2+) signaling, and cell growth and death. Recent discovery of the molecular identity of the mitochondrial Ca(2+) uniporter (MCU) provides new possibilities for application of genetic approaches to study the mitochondrial Ca(2+) influx mechanism in various cell types and tissues. In addition, the subsequent discovery of various auxiliary subunits associated with MCU suggests that mitochondrial Ca(2+) uptake is not solely regulated by a single protein (MCU), but likely by a macromolecular protein complex, referred to as the MCU-protein complex (mtCUC). Moreover, recent reports have shown the potential role of MCU posttranslational modifications in the regulation of mitochondrial Ca(2+) uptake through mtCUC. These observations indicate that mtCUCs form a local signaling complex at the inner mitochondrial membrane that could significantly regulate mitochondrial Ca(2+) handling, as well as numerous mitochondrial and cellular functions. In this review we discuss the current literature on mitochondrial Ca(2+) uptake mechanisms, with a particular focus on the structure and function of mtCUC, as well as its regulation by signal transduction pathways, highlighting current controversies and discrepancies.

  10. Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer's disease.

    Science.gov (United States)

    Hagl, Stephanie; Grewal, Rekha; Ciobanu, Ion; Helal, Amr; Khayyal, Mohamed T; Muller, Walter E; Eckert, Gunter P

    2015-01-01

    Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD. PMID:25125472

  11. Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

    Science.gov (United States)

    Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

    2014-06-01

    Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD(+) precursor, was previously shown to boost NAD(+) levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD(+) levels are a promising treatment strategy for mitochondrial myopathy. PMID:24711540

  12. Heart rate during aerobics classes in women with different previous experience of aerobics.

    Science.gov (United States)

    Laukkanen, R M; Kalaja, M K; Kalaja, S P; Holmala, E B; Paavolainen, L M; Tummavuori, M; Virtanen, P; Rusko, H K

    2001-01-01

    This study measured heart rate during floor and step aerobic classes at three intensity levels. A group of 20 female occasional exercisers [mean age 33 (SD 8) years, mean body mass index 21 (SD 2) kg.m-2 volunteered to participate in six aerobic classes (three floor classes, three step classes) and in a laboratory test as members of one of two groups according to their prestudy regular participation in aerobics classes. Subjects in group A had participated four or more times a week and those of group B less than twice a week. The characteristics of the groups were as follows: group A, n = 10, mean maximal oxygen uptake (VO2max) 38.7 (SD 3.6) ml.kg-1.min-1, mean maximal heart rate (HRmax) 183 (SD 8) beats.min-1; group B, n = 10, VO2max 36.1 (SD 3.6) ml.kg-1.min-1, HRmax 178 (SD 7) beats.min-1. Each class consisted of a warm-up, a 20 min period of structured aerobic exercise (cardiophase) and a cool-down. The cardiophase was planned and guided as light, (rate of perceived exertion, RPE 11-12), moderate (RPE 13-14) or heavy (RPE 15-17) by an experienced instructor. The mean heart rates during the light classes were 72 (step) and 74 (floor) %HRmax in group A and 75 (step) and 79 (floor) %HRmax in group B; during the moderate classes, 84 (step) and 80 (floor) %HRmax in group A and 82 (step) and 83 (floor) %HRmax in group B, and during the heavy classes 89 (step and floor) %HRmax in group A and 88 (step) and 92 (floor) %HRmax in group B. Differences in heart rate and %HRmax were not statistically significant between the groups. However, differences in heart rate and %HRmax between the intensities (light vs moderate, moderate vs heavy and light vs heavy) were significant within both groups (all, P < 0.01). Based on the results, we conclude that intensity management during the aerobics classes was generally successful regardless of the participants' prior participation in aerobics. However, some individuals who were older and/or had less prior participation tended to

  13. Mitochondrial transplantation for therapeutic use

    OpenAIRE

    McCully, James Donald; Levitsky, Sidney; del Nido, Pedro J.; Cowan, Douglas Burr

    2016-01-01

    Mitochondria play a key role in the homeostasis of the vast majority of the body’s cells. In the myocardium where mitochondria constitute 30 % of the total myocardial cell volume, temporary attenuation or obstruction of blood flow and as a result oxygen delivery to myocardial cells (ischemia) severely alters mitochondrial structure and function. These alterations in mitochondrial structure and function occur during ischemia and continue after blood flow and oxygen delivery to the myocardium i...

  14. Mitochondrial Dysfunction in Neurodegenerative Diseases

    OpenAIRE

    Johri, Ashu; Beal, M. Flint

    2012-01-01

    Neurodegenerative diseases are a large group of disabling disorders of the nervous system, characterized by the relative selective death of neuronal subtypes. In most cases, there is overwhelming evidence of impaired mitochondrial function as a causative factor in these diseases. More recently, evidence has emerged for impaired mitochondrial dynamics (shape, size, fission-fusion, distribution, movement etc.) in neurodegenerative diseases such as Parkinson's disease, Huntington's disease, amyo...

  15. A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology

    Directory of Open Access Journals (Sweden)

    Michelle T. Burstein

    2014-01-01

    Full Text Available A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.

  16. Is aerobic workload positively related to ambulatory blood pressure?

    DEFF Research Database (Denmark)

    Korshøj, Mette; Clays, Els; Lidegaard, Mark;

    2016-01-01

    PURPOSE: Cardiovascular disease is prevalent among workers with high levels of occupational physical activity. The increased risk may be due to a high relative aerobic workload, possibly leading to increased blood pressure. However, studies investigating the relation between relative aerobic...... workload and ambulatory blood pressure (ABP) are lacking. The aim was to explore the relationship between objectively measured relative aerobic workload and ABP. METHODS: A total of 116 cleaners aged 18-65 years were included after informed consent was obtained. A portable device (Spacelabs 90217...... relative aerobic workload and ABP were significant. CONCLUSIONS: Because workers may have an elevated relative aerobic workload for several hours each working day, this relationship may elucidate a mechanism behind the increased risk for cardiovascular disease among workers exposed to high levels...

  17. Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    was inhibited by buffering of intracellular calcium with BAPTA, by the antioxidant N-acetylcysteine and by uncoupling of mitochondrial oxidative phosphorylation from respiration with CCCP. These results indicate that Cd generate a prompt initiation of ROS production from mitochondria due to an increase...... peroxide (H2O2) has traditionally been regarded as toxic by-products of aerobic metabolism. However, recent findings indicate that H2O2 act as a signalling molecule. The aim of the present study was to monitor, in real time, the rates of ROS generation in order to directly determine their production...

  18. Mitochondrial efficiency and insulin resistance.

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Liverini, Giovanna; Iossa, Susanna

    2014-01-01

    Insulin resistance, "a relative impairment in the ability of insulin to exert its effects on glucose, protein and lipid metabolism in target tissues," has many detrimental effects on metabolism and is strongly correlated to deposition of lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial dysfunction in the onset of skeletal muscle insulin resistance has been proposed and many studies have dealt with possible alteration in mitochondrial function in obesity and diabetes, both in humans and animal models. Data reporting evidence of mitochondrial dysfunction in type two diabetes mellitus are numerous, even though the issue that this reduced mitochondrial function is causal in the development of the disease is not yet solved, also because a variety of parameters have been used in the studies carried out on this subject. By assessing the alterations in mitochondrial efficiency as well as the impact of this parameter on metabolic homeostasis of skeletal muscle cells, we have obtained results that allow us to suggest that an increase in mitochondrial efficiency precedes and therefore can contribute to the development of high-fat-induced insulin resistance in skeletal muscle. PMID:25601841

  19. Mitochondrial Metabolism in Aging Heart.

    Science.gov (United States)

    Lesnefsky, Edward J; Chen, Qun; Hoppel, Charles L

    2016-05-13

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area, there is ≈50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  20. Mitochondrial Epigenetics and Environmental Exposure.

    Science.gov (United States)

    Lambertini, Luca; Byun, Hyang-Min

    2016-09-01

    The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration. PMID:27344144

  1. Mitochondrial dysfunction in Parkinson's disease.

    Science.gov (United States)

    Hu, Qingsong; Wang, Guanghui

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, which is characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta and the formation of Lewy bodies and Lewy neurites in surviving DA neurons in most cases. Although the cause of PD is still unclear, the remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. Numerous studies showed that dysfunction of mitochondria may play key roles in DA neuronal loss. Both genetic and environmental factors that are associated with PD contribute to mitochondrial dysfunction and PD pathogenesis. The induction of PD by neurotoxins that inhibit mitochondrial complex I provides direct evidence linking mitochondrial dysfunction to PD. Decrease of mitochondrial complex I activity is present in PD brain and in neurotoxin- or genetic factor-induced PD cellular and animal models. Moreover, PINK1 and parkin, two autosomal recessive PD gene products, have important roles in mitophagy, a cellular process to clear damaged mitochondria. PINK1 activates parkin to ubiquitinate outer mitochondrial membrane proteins to induce a selective degradation of damaged mitochondria by autophagy. In this review, we summarize the factors associated with PD and recent advances in understanding mitochondrial dysfunction in PD. PMID:27453777

  2. CFTR activity and mitochondrial function

    Directory of Open Access Journals (Sweden)

    Angel Gabriel Valdivieso

    2013-01-01

    Full Text Available Cystic Fibrosis (CF is a frequent and lethal autosomal recessive disease, caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR. Before the discovery of the CFTR gene, several hypotheses attempted to explain the etiology of this disease, including the possible role of a chloride channel, diverse alterations in mitochondrial functions, the overexpression of the lysosomal enzyme α-glucosidase and a deficiency in the cytosolic enzyme glucose 6-phosphate dehydrogenase. Because of the diverse mitochondrial changes found, some authors proposed that the affected gene should codify for a mitochondrial protein. Later, the CFTR cloning and the demonstration of its chloride channel activity turned the mitochondrial, lysosomal and cytosolic hypotheses obsolete. However, in recent years, using new approaches, several investigators reported similar or new alterations of mitochondrial functions in Cystic Fibrosis, thus rediscovering a possible role of mitochondria in this disease. Here, we review these CFTR-driven mitochondrial defects, including differential gene expression, alterations in oxidative phosphorylation, calcium homeostasis, oxidative stress, apoptosis and innate immune response, which might explain some characteristics of the complex CF phenotype and reveals potential new targets for therapy.

  3. Profiles of nuclear and mitochondrial encoded mRNAs in developing and quiescent embryos of Artemia franciscana.

    Science.gov (United States)

    Hardewig, I; Anchordoguy, T J; Crawford, D L; Hand, S C

    1996-05-24

    Embryos of the brine shrimp Artemia franciscana are able to withstand long bouts of environmental anoxia by entering a quiescent state during which metabolism is greatly depressed. Recent evidence supports a global arrest of protein synthesis during quiescence. In this study we measured the amounts of mRNA for a mitochondrial-encoded subunit of cytochrome c oxidase (COX I) and for nuclear-encoded actin during aerobic development, anaerobiosis, and aerobic acidosis (artificial quiescence imposed by intracellular acidification under aerobic conditions). The levels of both COX I and actin transcripts increased significantly during aerobic development. COX I mRNA levels were tightly correlated with previous measures of COX catalytic activity, which suggests that COX synthesis could be regulated by message concentration during aerobic development. The ontogenetic increase for these mRNAs was blocked by anoxia and aerobic acidosis. Importantly, the levels of COX I and actin mRNA did not decline appreciably during the 6 h bouts of quiescence, even though protein synthesis is acutely arrested by these same treatments. Thus, the constancy of mRNA levels during quiescence indicate that reduced protein synthesis is not caused by message limitation, but rather, is likely controlled at the translational level. One advantage of this regulatory mechanism is the conservation of mRNA molecules during quiescence, which would potentially favor a quick resumption of translation as soon as oxygen is returned to the embryos. Finally, because anoxia and aerobic acidosis are both characterized by acidic intracellular pH, the reduction in pH may serve, directly or indirectly, as one signal regulating levels of mRNA in this embryo during quiescence. PMID:8817476

  4. Primary clear cell renal carcinoma cells display minimal mitochondrial respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition by 3-Bromopyruvate.

    Science.gov (United States)

    Nilsson, H; Lindgren, D; Mandahl Forsberg, A; Mulder, H; Axelson, H; Johansson, M E

    2015-01-01

    Changes of cellular metabolism are an integral property of the malignant potential of most cancer cells. Already in the 1930s, Otto Warburg observed that tumor cells preferably utilize glycolysis and lactate fermentation for energy production, rather than the mitochondrial oxidative phosphorylation dominating in normal cells, a phenomenon today known as the Warburg effect. Even though many tumor types display a high degree of aerobic glycolysis, they still retain the activity of other energy-producing metabolic pathways. One exception seems to be the clear cell variant of renal cell carcinoma, ccRCC, where the activity of most other pathways than that of glycolysis has been shown to be reduced. This makes ccRCC a promising candidate for the use of glycolytic inhibitors in treatment of the disease. However, few studies have so far addressed this issue. In this report, we show a strikingly reduced mitochondrial respiratory capacity of primary human ccRCC cells, resulting in enhanced sensitivity to glycolytic inhibition by 3-Bromopyruvate (3BrPA). This effect was largely absent in established ccRCC cell lines, a finding that highlights the importance of using biologically relevant models in the search for new candidate cancer therapies. 3BrPA markedly reduced ATP production in primary ccRCC cells, followed by cell death. Our data suggest that glycolytic inhibitors such as 3BrPA, that has been shown to be well tolerated in vivo, should be further analyzed for the possible development of selective treatment strategies for patients with ccRCC. PMID:25569102

  5. Mechanistic insight from the crystal structure of mitochondrial complex I

    NARCIS (Netherlands)

    Zickermann, V.; Wirth, C.; Nasiri, H.; Siegmund, K.; Schwalbe, H.; Hunte, C.; Brandt, U.

    2015-01-01

    Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complicated membrane protein complexes. The enzyme contributes substantially to oxidative energy conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders

  6. Aerobic rice: crop performance and water use efficiency

    Directory of Open Access Journals (Sweden)

    Chiara Grassi

    2011-11-01

    Full Text Available Rice (Oryza sativa production largely depends on traditional flooded rice systems whose sustainability is threatened by a progressive decrease in water availability and a constant increase in rice demand due to strong demographic boom in world population. A newly developed water-saving rice system is aerobic rice in which rice grows in nonflooded and unsaturated soil. From 2001, at the International Rice Research Institute in the Philippines, this system has been monitored to identify potentially promising varieties of rice able to grow as an irrigated upland crop and quantify yield potential and water use efficiency. This study reports on the results of cultivating the upland rice variety Apo under different water conditions in 2004-2005 at the IRRI farm in both the dry and wet seasons. The water treatments considered were: aerobic and flooded conditions, alternated flooded and aerobic conditions and aerobic after fallow. Yield and water productivity were compared between aerobic and flooded treatment in both seasons, with the objective of analysing the differences between water treatments. In the experiment the effect of different nitrogen (N application is also considered. The results indicate that the aerobic rice yield was lower than rice production under flood treatment, confirming that observed over past years. Nevertheless, when the aerobic condition is alternated with the anaerobic condition, or a fallow period, the production under aerobic treatment provides good yields (respectively 4.2 and 4.4 ha-1. The fallow period was introduced to observe the response of rice grown under this management. Water productivity was higher in aerobic fields, especially after fallow (0.88 g kg-1. The nitrogen application induced an increase in yield and water productivity, partially compensating for the lack of water in aerobic fields.

  7. The effect of sulfide on the aerobic corrosion of carbon steel in near-neutral pH saline solutions

    International Nuclear Information System (INIS)

    Highlights: ► The corrosion rate is low when steel is exposed to anaerobic conditions (pH = 8.9). ► An anaerobic to aerobic corrosion with sulfide switch increases the corrosion rate. ► Aerobic exposure induces the formation of goethite-covered tubercles. ► Continual sulfide exposure leads to the slow conversion of goethite to mackinawite. - Abstract: Severe corrosion damage may occur when gas transmission pipelines are exposed, at disbonded coating locations, to trapped waters containing sulfide followed by secondary exposure to air. Aerobic corrosion with sulfide was investigated in a long-term corrosion experiment in which corrosion was monitored by measurement of the corrosion potential and polarization resistance obtained from linear polarization resistance measurements. The properties and composition of the corrosion product deposits formed were determined using scanning electron microscopy, energy dispersive X-ray analysis, and Raman spectroscopy. A switch from aerobic to aerobic-with-sulfide corrosion doubles the relative corrosion rate.

  8. Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function.

    Science.gov (United States)

    Irwin, R W; Yao, J; To, J; Hamilton, R T; Cadenas, E; Brinton, R D

    2012-01-01

    The mitochondrial energy-transducing capacity of the brain is important for long-term neurological health and is influenced by endocrine hormone responsiveness. The present study aimed to determine the role of oestrogen receptor (ER) subtypes in regulating mitochondrial function using selective agonists for ERα (propylpyrazoletriol; PPT) and ERβ (diarylpropionitrile; DPN). Ovariectomised female rats were treated with 17β-oestradiol (E(2) ), PPT, DPN or vehicle control. Both ER selective agonists significantly increased the mitochondrial respiratory control ratio and cytochrome oxidase (COX) activity relative to vehicle. Western blots of purified whole brain mitochondria detected ERα and, to a greater extent, ERβ localisation. Pre-treatment with DPN, an ERβ agonist, significantly increased ERβ association with mitochondria. In the hippocampus, DPN activated mitochondrial DNA-encoded COX I expression, whereas PPT was ineffective, indicating that mechanistically ERβ, and not ERα, activated mitochondrial transcriptional machinery. Both selective ER agonists increased protein expression of nuclear DNA-encoded COX IV, suggesting that activation of ERβ or ERα is sufficient. Selective ER agonists up-regulated a panel of bioenergetic enzymes and antioxidant defence proteins. Up-regulated proteins included pyruvate dehydrogenase, ATP synthase, manganese superoxide dismutase and peroxiredoxin V. In vitro, whole cell metabolism was assessed in live primary cultured hippocampal neurones and mixed glia. The results of analyses conducted in vitro were consistent with data obtained in vivo. Furthermore, lipid peroxides, accumulated as a result of hormone deprivation, were significantly reduced by E(2) , PPT and DPN. These findings suggest that the activation of both ERα and ERβ is differentially required to potentiate mitochondrial function in brain. As active components in hormone therapy, synthetically designed oestrogens as well as natural phyto-oestrogen cocktails

  9. Aerobic Exercise Recovers Disuse-induced Atrophy Through the Stimulus of the LRP130/PGC-1α Complex in Aged Rats.

    Science.gov (United States)

    Vechetti-Junior, Ivan J; Bertaglia, Raquel S; Fernandez, Geysson J; de Paula, Tassiana G; de Souza, Rodrigo W A; Moraes, Leonardo N; Mareco, Edson A; de Freitas, Carlos E A; Aguiar, Andreo F; Carvalho, Robson F; Dal-Pai-Silva, Maeli

    2016-05-01

    Physical training has been shown to be important to the control of muscle mass during aging, through the activation of several pathways including, IGF1-AKT and PGC-1α. Also, it was demonstrated that LRP130, a component of the PGC-1α complex, is important for the PGC-1α-dependent transcription of several mitochondrial genes in vivo. To explore the role of physical training during aging, we investigated the effects on muscle recovery after short-term immobilization followed by 3 or 7 days with aerobic or resistance training. Using morphological (myofibrillar adenosine triphosphatase activity, to assess the total muscle fiber cross-sectional area (CSA) and the frequency of specific fiber types), biochemical (myosin heavy chain), and molecular analyses (quantitative real-time PCR, functional pathways analyses, and Western blot), our results indicated that after an atrophic stimulus, only animals subjected to aerobic training showed entire recovery of cross-sectional area; aerobic training reduced the ubiquitin-proteasome system components involved in muscle atrophy after 3 days of recovery, and the upregulation in PGC-1α expression enhanced the process of muscle recovery by inhibiting the FoxO pathway, with the possible involvement of LRP130. These results suggest that aerobic training enhanced the muscle regeneration process after disuse-induced atrophy in aged rats possibly through of the LRP130/PGC-1α complex by inhibiting the ubiquitin-proteasome system. PMID:25991827

  10. The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications.

    Science.gov (United States)

    Brinton, Roberta Diaz

    2008-10-01

    The 'healthy cell bias of estrogen action' hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. Estrogen-induced signaling pathways in hippocampal and cortical neurons converge upon the mitochondria to enhance aerobic glycolysis coupled to the citric acid cycle, mitochondrial respiration and ATP generation. Convergence of estrogen-induced signaling onto mitochondria is also a point of vulnerability when activated in diseased neurons which exacerbates degeneration through increased load on dysregulated calcium homeostasis. As the continuum of neurological health progresses from healthy to unhealthy so too do the benefits of estrogen or hormone therapy. The healthy cell bias of estrogen action hypothesis provides a lens through which to assess disparities in outcomes across basic and clinical science and on which to predict outcomes of estrogen interventions for sustaining neurological health and preventing age-associated neurodegenerative diseases such as Alzheimer's.

  11. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

    Science.gov (United States)

    Marcovina, Santica M; Sirtori, Cesare; Peracino, Andrea; Gheorghiade, Mihai; Borum, Peggy; Remuzzi, Giuseppe; Ardehali, Hossein

    2013-02-01

    Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential. PMID:23138103

  12. Aerobics trainer, health club settle discrimination lawsuit.

    Science.gov (United States)

    1995-04-01

    A health club settled out-of-court, agreeing to pay an undisclosed sum of money and to train its managers on the legal obligations of people with HIV and other disabilities, following litigation brought by an aerobics instructor at the club. The instructor filed the suit after he was forced to either disclose his HIV status to the 3,000 members or be fired. He was fired after he refused to sign a letter drafted by the club's manager. Six months later the club's president gave club employees the letter which the plaintiff argued violated his right to privacy. This is the second time a health club has settled an AIDS discrimination case. Both cases focused on the Americans with Disabilities Act (ADA). In settling the case, the club denied any wrongdoing and said they settled out of court to avoid the costs of litigation. PMID:11362274

  13. Aerobic exercises: their cardiovascular and other benefits

    International Nuclear Information System (INIS)

    Aerobic exercise can help prevent ischemic heart disease and other diseases. Physical inactivity is a major factor for developing Coronary Artery Disease (CAD) which is characterized by deposit of cholesterol, calcium and other substances in the inner lining of the arteries, that supply to cardiac muscle. It also contributes to other risk factors including obesity, hypertension, increased triglycerides, low level of HDL cholesterol and diabetes. The essential components of a systematic individualized exercise prescription include the appropriate mode, intensity, duration, frequency and progression of physical activity. There are four components of exercise program; a warm up, an endurance phase, optional recreational activity and a cool down. For sedentary individuals, exercise should start at 60% of maximum heart rare. Benefits of physical activity depend on the total amount of exercise. Vigorous leisure time activity should be promoted in order to give way to healthy living. (author)

  14. Aerobic growth at nanomolar oxygen concentrations

    DEFF Research Database (Denmark)

    Stolper, Daniel; Revsbech, Niels Peter; Canfield, Donald Eugene

    2010-01-01

    known. These capabilities also provide a framework for reconstructing a critical period in the history of life, because low, but not negligible, atmospheric oxygen levels could have persisted before the "Great Oxidation" of the Earth's surface about 2.3 to 2.4 billion years ago. Here, we show......Molecular oxygen (O2) is the second most abundant gas in the Earth's atmosphere, but in many natural environments, its concentration is reduced to low or even undetectable levels. Although low-oxygen-adapted organisms define the ecology of low-oxygen environments, their capabilities are not fully...... that Escherichia coli K-12, chosen for its well-understood biochemistry, rapid growth rate, and low-oxygen-affinity terminal oxidase, grows at oxygen levels of ≤ 3 nM, two to three orders of magnitude lower than previously observed for aerobes. Our study expands both the environmental range and temporal history...

  15. Aerobic growth at nanomolar oxygen concentrations

    DEFF Research Database (Denmark)

    Stolper, Daniel Aaron; Revsbech, Niels Peter; Canfield, Donald Eugene

    2010-01-01

    known. These capabilities also provide a framework for reconstructing a critical period in the history of life, because low, but not negligible, atmospheric oxygen levels could have persisted before the “Great Oxidation” of the Earth’s surface about 2.3 to 2.4 billion years ago. Here, we show......Molecular oxygen (O2) is the second most abundant gas in the Earth’s atmosphere, but in many natural environments, its concentration is reduced to low or even undetectable levels. Although low-oxygen-adapted organisms define the ecology of low-oxygen environments, their capabilities are not fully...... that Escherichia coli K-12, chosen for its well-understood biochemistry, rapid growth rate, and low-oxygen-affinity terminal oxidase, grows at oxygen levels of ≤ 3 nM, two to three orders of magnitude lower than previously observed for aerobes. Our study expands both the environmental range and temporal history...

  16. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    NARCIS (Netherlands)

    Rooijers, K.; Loayza-Puch, F.; Nijtmans, L.G.J.; Agami, R.

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations oft

  17. Mitochondrial bioenergetics in young, adult, middle-age and senescent brown Norway rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and may play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identi...

  18. Effects of Kettlebell Training on Aerobic Capacity.

    Science.gov (United States)

    Falatic, J Asher; Plato, Peggy A; Holder, Christopher; Finch, Daryl; Han, Kyungmo; Cisar, Craig J

    2015-07-01

    This study examined the effects of a kettlebell training program on aerobic capacity. Seventeen female National Collegiate Athletic Association Division I collegiate soccer players (age: 19.7 ± 1.0 years, height: 166.1 ± 6.4 cm, weight: 64.2 ± 8.2 kg) completed a graded exercise test to determine maximal oxygen consumption (V̇O2max). Participants were assigned to a kettlebell intervention group (KB) (n = 9) or a circuit weight-training (CWT) control group (n = 8). Participants in the KB group completed a kettlebell snatch test to determine individual snatch repetitions. Both groups trained 3 days a week for 4 weeks in addition to their off-season strength and conditioning program. The KB group performed the 15:15 MVO2 protocol (20 minutes of kettlebell snatching with 15 seconds of work and rest intervals). The CWT group performed multiple free-weight and dynamic body-weight exercises as part of a continuous circuit program for 20 minutes. The 15:15 MVO2 protocol significantly increased V̇O2max in the KB group. The average increase was 2.3 ml·kg⁻¹·min⁻¹, or approximately a 6% gain. There was no significant change in V̇O2max in the CWT control group. Thus, the 4-week 15:15 MVO2 kettlebell protocol, using high-intensity kettlebell snatches, significantly improved aerobic capacity in female intercollegiate soccer players and could be used as an alternative mode to maintain or improve cardiovascular conditioning. PMID:26102260

  19. Integrated anaerobic/aerobic biological treatment for intensive swine production.

    Science.gov (United States)

    Bortone, Giuseppe

    2009-11-01

    Manure processing could help farmers to effectively manage nitrogen (N) surplus load. Many pig farms have to treat wastewater. Piggery wastewater treatment is a complex challenge, due to the high COD and N concentrations and low C/N ratio. Anaerobic digestion (AD) could be a convenient pre-treatment, particularly from the energetic view point and farm income, but this causes further reduction of C/N ratio and makes denitrification difficult. N removal can only be obtained integrating anaerobic/aerobic treatment by taking into account the best use of electron donors. Experiences gained in Italy during development of integrated biological treatment approaches for swine manure, from bench to full scale, are reported in this paper. Solid/liquid separation as pre-treatment of raw manure is an efficient strategy to facilitate liquid fraction treatment without significantly lowering C/N ratio. In Italy, two full scale SBRs showed excellent efficiency and reliability. Current renewable energy policy and incentives makes economically attractive the application of AD to the separated solid fraction using high solid anaerobic digester (HSAD) technology. Economic evaluation showed that energy production can reduce costs up to 60%, making sustainable the overall treatment. PMID:19135363

  20. Protons and pleomorphs: aerobic hydrogen production in Azotobacters.

    Science.gov (United States)

    Noar, Jesse D; Bruno-Bárcena, José M

    2016-02-01

    As obligate aerobic soil organisms, the ability of Azotobacter species to fix nitrogen is unusual given that the nitrogenase complex requires a reduced cellular environment. Molecular hydrogen is an unavoidable byproduct of the reduction of dinitrogen; at least one molecule of H2 is produced for each molecule of N2 fixed. This could be considered a fault in nitrogenase efficiency, essentially a waste of energy and reducing equivalents. Wild-type Azotobacter captures this hydrogen and oxidizes it with its membrane-bound uptake hydrogenase complex. Strains lacking an active hydrogenase complex have been investigated for their hydrogen production capacities. What is the role of H2 in the energy metabolism of nitrogen-fixing Azotobacter? Is hydrogen production involved in Azotobacter species' protection from or tolerance to oxygen, or vice versa? What yields of hydrogen can be expected from hydrogen-evolving strains? Can the yield of hydrogen be controlled or increased by changing genetic, environmental, or physiological conditions? We will address these questions in the following mini-review.

  1. Removal of Cr3+ from aqueous solution by biosorption with aerobic granules

    International Nuclear Information System (INIS)

    Aerobic granules were utilized as an effective biosorbent to remove Cr3+ from aqueous solution. The results showed that the initial pH, contact time, and Cr3+ concentration affected the biosorption process significantly. Both Freundlich and Langmuir isotherms were able to describe the equilibrium data reasonably with high correlation coefficients (R2 > 0.95) and pseudo-second-order model best fitted the biosorption process at experimental conditions. Moreover, Environmental Scanning Electronic microscope (ESEM), X-ray energy dispersion (EDX), and Fourier transform infrared (FTIR) analyses revealed that metal complexation, chemical precipitation, and ion exchange were involved in the removal of Cr3+ with aerobic granules. Further analysis by a metal ion fraction test demonstrated that metal complexation could be the dominant mechanism of biosorption, whereas chemical precipitation and ion exchange appeared only to have minor role in the overall Cr3+ biosorption process.

  2. Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging

    Directory of Open Access Journals (Sweden)

    Lisa Staunton

    2011-01-01

    Full Text Available Mitochondria are of central importance for energy generation in skeletal muscles. Expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis, fibre maturation, and various neuromuscular pathologies, as well as natural fibre aging. Mass spectrometry-based proteomics suggests itself as a convenient large-scale and high-throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease. This paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles. Changes in the abundance, biochemical activity, subcellular localization, and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel biomarkers of aging. In the long term, this may advance diagnostic procedures, improve the monitoring of disease progression, help in the testing of side effects due to new drug regimes, and enhance our molecular understanding of age-related muscle degeneration.

  3. Mitochondrial DNA as a potential tool for early cancer detection

    Directory of Open Access Journals (Sweden)

    Parr Ryan L

    2006-01-01

    Full Text Available Abstract The recent surge in mitochondrial research has been driven by the identification of mitochondria-associated diseases and the role of mitochondria in apoptosis. Both of these aspects have identified mitochondrial analysis as a vital component of medical research. Moreover, mitochondria have been implicated in the process of carcinogenesis because of their vital role in energy production, nuclear-cytoplasmic signal integration and control of metabolic pathways. Interestingly, at some point during neoplastic transformation, there is an increase in reactive oxygen species, which damage the mitochondrial genome. This accelerates the somatic mutation rate of mitochondrial DNA. It has been proposed that these mutations may serve as an early indication of potential cancer development and may represent a means for tracking tumour progression. The purpose of this review is to explore the potential utility that these mutations may afford for the identification and monitoring of neoplasia and malignant transformation where appropriate body fluids or non-invasive tissue access is available for mitochondrial DNA recovery. Specifically, prostate, breast, colorectal, skin and lung cancers are discussed.

  4. Melatonin: A Potential Anti-Oxidant Therapeutic Agent for Mitochondrial Dysfunctions and Related Disorders.

    Science.gov (United States)

    Ganie, Showkat Ahmad; Dar, Tanveer Ali; Bhat, Aashiq Hussain; Dar, Khalid B; Anees, Suhail; Zargar, Mohammad Afzal; Masood, Akbar

    2016-02-01

    Mitochondria play a central role in cellular physiology. Besides their classic function of energy metabolism, mitochondria are involved in multiple cell functions, including energy distribution through the cell, energy/heat modulation, regulation of reactive oxygen species (ROS), calcium homeostasis, and control of apoptosis. Simultaneously, mitochondria are the main producer and target of ROS with the result that multiple mitochondrial diseases are related to ROS-induced mitochondrial injuries. Increased free radical generation, enhanced mitochondrial inducible nitric oxide synthase (iNOS) activity, enhanced nitric oxide (NO) production, decreased respiratory complex activity, impaired electron transport system, and opening of mitochondrial permeability transition pores have all been suggested as factors responsible for impaired mitochondrial function. Because of these, neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and aging, are caused by ROS-induced mitochondrial dysfunctions. Melatonin, the major hormone of the pineal gland, also acts as an anti-oxidant and as a regulator of mitochondrial bioenergetic function. Melatonin is selectively taken up by mitochondrial membranes, a function not shared by other anti-oxidants, and thus has emerged as a major potential therapeutic tool for treating neurodegenerative disorders. Multiple in vitro and in vivo experiments have shown the protective role of melatonin for preventing oxidative stress-induced mitochondrial dysfunction seen in experimental models of PD, AD, and HD. With these functions in mind, this article reviews the protective role of melatonin with mechanistic insights against mitochondrial diseases and suggests new avenues for safe and effective treatment modalities against these devastating neurodegenerative diseases. Future insights are also discussed. PMID:26087000

  5. Mitochondrial drug targets in neurodegenerative diseases.

    Science.gov (United States)

    Lee, Jiyoun

    2016-02-01

    Growing evidence suggests that mitochondrial dysfunction is the main culprit in neurodegenerative diseases. Given the fact that mitochondria participate in diverse cellular processes, including energetics, metabolism, and death, the consequences of mitochondrial dysfunction in neuronal cells are inevitable. In fact, new strategies targeting mitochondrial dysfunction are emerging as potential alternatives to current treatment options for neurodegenerative diseases. In this review, we focus on mitochondrial proteins that are directly associated with mitochondrial dysfunction. We also examine recently identified small molecule modulators of these mitochondrial targets and assess their potential in research and therapeutic applications.

  6. Formation and Regulation of Mitochondrial Membranes

    Directory of Open Access Journals (Sweden)

    Laila Cigana Schenkel

    2014-01-01

    Full Text Available Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases.

  7. Short term aerobic exercise alters the reinforcing value of food in inactive adults.

    Science.gov (United States)

    Panek, Leah M; Jones, Kelly R; Temple, Jennifer L

    2014-10-01

    Motivation to eat, or the reinforcing value of food, may be influenced by a number of factors, including physical activity. The purpose of these studies was to test the hypothesis that short-term moderate-vigorous intensity aerobic exercise would alter the reinforcing value of high (HED) and low (LED) energy density foods in inactive adults. The reinforcing value of LED and HED food was measured at baseline and again after two weeks of aerobic exercise. In Experiment 1, 41 participants were randomized to a no exercise condition or aerobic exercise for 3 days per week for two weeks. In Experiment 2, 76 participants were randomized to one of four aerobic exercise frequencies, 0, 1, 3, or 5 days per week for two weeks. In both experiments, exercise reduced the reinforcing value of HED food compared to baseline and to non-exercise controls. In Experiment 2, the 5 day group also showed a significant increase in the reinforcing value of LED food compared to baseline and other exercise frequencies. Liking of HED and LED foods and consumption of HED food were not affected by exercise treatment. Finally, in Experiment 2, the 5 day group reported consuming more energy outside of the laboratory than the other groups. Taken together, these data suggest, in inactive individuals, motivation to obtain HED and LED foods can be altered with a short-term moderate-vigorous intensity exercise intervention. Further research is needed to understand the cognitive and physiological processes involved in food choices paired with exercise.

  8. Contribution of anaerobic energy expenditure to whole body thermogenesis

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    Scott Christopher B

    2005-06-01

    Full Text Available Abstract Heat production serves as the standard measurement for the determination of energy expenditure and efficiency in animals. Estimations of metabolic heat production have traditionally focused on gas exchange (oxygen uptake and carbon dioxide production although direct heat measurements may include an anaerobic component particularly when carbohydrate is oxidized. Stoichiometric interpretations of the ratio of carbon dioxide production to oxygen uptake suggest that both anaerobic and aerobic heat production and, by inference, all energy expenditure – can be accounted for with a measurement of oxygen uptake as 21.1 kJ per liter of oxygen. This manuscript incorporates contemporary bioenergetic interpretations of anaerobic and aerobic ATP turnover to promote the independence of these disparate types of metabolic energy transfer: each has different reactants and products, uses dissimilar enzymes, involves different types of biochemical reactions, takes place in separate cellular compartments, exploits different types of gradients and ultimately each operates with distinct efficiency. The 21.1 kJ per liter of oxygen for carbohydrate oxidation includes a small anaerobic heat component as part of anaerobic energy transfer. Faster rates of ATP turnover that exceed mitochondrial respiration and that are supported by rapid glycolytic phosphorylation with lactate production result in heat production that is independent of oxygen uptake. Simultaneous direct and indirect calorimetry has revealed that this anaerobic heat does not disappear when lactate is later oxidized and so oxygen uptake does not adequately measure anaerobic efficiency or energy expenditure (as was suggested by the "oxygen debt" hypothesis. An estimate of anaerobic energy transfer supplements the measurement of oxygen uptake and may improve the interpretation of whole-body energy expenditure.

  9. Hsp90 inhibition decreases mitochondrial protein turnover.

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    Daciana H Margineantu

    Full Text Available BACKGROUND: Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial morphology, with ultimate compromise of mitochondrial integrity and apoptosis. FINDINGS: We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP. CONCLUSIONS: Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors.

  10. Heritability of aerobic power of individuals in northeast Brazil.

    Science.gov (United States)

    Alonso, L; Souza, Ec; Oliveira, Mv; do Nascimento, Lfe; Dantas, Pms

    2014-12-01

    The objective of this study was to evaluate the genetic and environmental contribution to variation in aerobic power in monozygotic (MZ) and dizygotic (DZ) twins. The sample consisted of 20 MZ individuals (12 females and 8 males) and 16 DZ individuals (12 females and 4 males), aged from 8 to 26 years, residents in Natal, Rio Grande do Norte. The twins were assessed by a multistage fitness test. The rate of heritability found for aerobic power was 77%. Based on the results, the estimated heritability was largely responsible for the differences in aerobic power. This implies that such measures are under strong genetic influence.

  11. Metabolic Inflexibility: When Mitochondrial Indecision Leads to Metabolic Gridlock

    OpenAIRE

    Muoio, Deborah M.

    2014-01-01

    Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By cont...

  12. Yeast as a Tool to Study Signaling Pathways in Mitochondrial Stress Response and Cytoprotection

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    Maša Ždralević

    2012-01-01

    Full Text Available Cell homeostasis results from the balance between cell capability to adapt or succumb to environmental stress. Mitochondria, in addition to supplying cellular energy, are involved in a range of processes deciding about cellular life or death. The crucial role of mitochondria in cell death is well recognized. Mitochondrial dysfunction has been associated with the death process and the onset of numerous diseases. Yet, mitochondrial involvement in cellular adaptation to stress is still largely unexplored. Strong interest exists in pharmacological manipulation of mitochondrial metabolism and signaling. The yeast Saccharomyces cerevisiae has proven a valuable model organism in which several intracellular processes have been characterized in great detail, including the retrograde response to mitochondrial dysfunction and, more recently, programmed cell death. In this paper we review experimental evidences of mitochondrial involvement in cytoprotection and propose yeast as a model system to investigate the role of mitochondria in the cross-talk between prosurvival and prodeath pathways.

  13. Mitochondria poised at a fission-fusion balance?: A quantitative assessment of mitochondrial network complexity

    CERN Document Server

    Zamponi, Nahuel; Billoni, Orlando V; Cannas, Sergio A; Helguera, Pablo R; Chialvo, Dante R

    2016-01-01

    Mitochondrial networks have been shown to exhibit a variety of complex behaviors, including cell-wide oscillations of mitochondrial energy states, as well as a phase transition in response to oxidative stress. Since functional status and structural properties are often intertwined, in this work we look at the structural properties of the organelle in normal mouse embryonic fibroblasts, describing its most relevant features. Subsequently we manipulated mitochondrial morphology using two interventions with opposite effects: over-expression of mitofusin 1, a protein that promotes mitochondria fusion, and paraquat treatment, a compound that induces mitochondrial fragmentation due to oxidative stress. Quantitative analysis of the organelle's structural clusters revealed that healthy mitochondrial networks were in a status intermediate between the extremes of highly fragmented and completely fusioned networks. This was confirmed by a comparison of our empirical findings with those of a recently described computatio...

  14. Curcumin, mitochondrial biogenesis, and mitophagy: Exploring recent data and indicating future needs.

    Science.gov (United States)

    de Oliveira, Marcos Roberto; Jardim, Fernanda Rafaela; Setzer, William N; Nabavi, Seyed Mohammad; Nabavi, Seyed Fazel

    2016-01-01

    Mitochondria are dynamic double-membrane bound organelles which have key roles in a variety of cellular functions such as energy producing, regulation of calcium flux, cellular stress responses including autophagy and apoptosis. A growing body of evidence indicates that mitochondrial dysfunction is the main culprit in a myriad of diseases such as neurodegenerative disease. This fact opens a new therapeutic window based on targeting mitochondrial dysfunction for treatment of these diseases. Recently an abundance of evidence shows the promising role of polyphenolic compounds on mitochondrial structure and function. Curcumin, a well-known polyphenolic compound, is an abundant component of turmeric. The promising roles of curcumin against different diseases are highly publicized. The aim of the present work is to critically review the scientific evidence to provide a clear view of how curcumin improves mitochondrial dynamics regarding mitochondrial biogenesis and mitophagy. We also present curcumin biosynthesis, source, bioavailability and metabolism in order to give an overview of this compound. PMID:27143655

  15. Impaired Cerebral Mitochondrial Oxidative Phosphorylation Function in a Rat Model of Ventricular Fibrillation and Cardiopulmonary Resuscitation

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    Jun Jiang

    2014-01-01

    Full Text Available Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA. Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF. We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP and phosphocreatine (PCr developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

  16. Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins.

    Science.gov (United States)

    Neufeld-Cohen, Adi; Robles, Maria S; Aviram, Rona; Manella, Gal; Adamovich, Yaarit; Ladeuix, Benjamin; Nir, Dana; Rousso-Noori, Liat; Kuperman, Yael; Golik, Marina; Mann, Matthias; Asher, Gad

    2016-03-22

    Mitochondria are major suppliers of cellular energy through nutrients oxidation. Little is known about the mechanisms that enable mitochondria to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. To address this question, we applied MS-based quantitative proteomics on isolated mitochondria from mice killed throughout the day and identified extensive oscillations in the mitochondrial proteome. Remarkably, the majority of cycling mitochondrial proteins peaked during the early light phase. We found that rate-limiting mitochondrial enzymes that process lipids and carbohydrates accumulate in a diurnal manner and are dependent on the clock proteins PER1/2. In this conjuncture, we uncovered daily oscillations in mitochondrial respiration that peak during different times of the day in response to different nutrients. Notably, the diurnal regulation of mitochondrial respiration was blunted in mice lacking PER1/2 or on a high-fat diet. We propose that PERIOD proteins optimize mitochondrial metabolism to daily changes in energy supply/demand and thereby, serve as a rheostat for mitochondrial nutrient utilization. PMID:26862173

  17. The order of exercise during concurrent training for rehabilitation does not alter acute genetic expression, mitochondrial enzyme activity or improvements in muscle function.

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    Lauren G MacNeil

    Full Text Available Concurrent exercise combines different modes of exercise (e.g., aerobic and resistance into one training protocol, providing stimuli meant to increase muscle strength, aerobic capacity and mass. As disuse is associated with decrements in strength, aerobic capacity and muscle size concurrent training is an attractive modality for rehabilitation. However, interference between the signaling pathways may result in preferential improvements for one of the exercise modes. We recruited 18 young adults (10 ♂, 8 ♀ to determine if order of exercise mode during concurrent training would differentially affect gene expression, protein content and measures of strength and aerobic capacity after 2 weeks of knee-brace induced disuse. Concurrent exercise sessions were performed 3x/week for 6 weeks at gradually increasing intensities either with endurance exercise preceding (END>RES or following (RES>END resistance exercise. Biopsies were collected from the vastus lateralis before, 3 h after the first exercise bout and 48 h after the end of training. Concurrent exercise altered the expression of genes involved in mitochondrial biogenesis (PGC-1α, PRC, PPARγ, hypertrophy (PGC-1α4, REDD2, Rheb and atrophy (MuRF-1, Runx1, increased electron transport chain complex protein content, citrate synthase and mitochondrial cytochrome c oxidase enzyme activity, muscle mass, maximum isometric strength and VO 2peak. However, the order in which exercise was completed (END>RES or RES>END only affected the protein content of mitochondrial complex II subunit. In conclusion, concurrent exercise training is an effective modality for the rehabilitation of the loss of skeletal muscle mass, maximum strength, and peak aerobic capacity resulting from disuse, regardless of the order in which the modes of exercise are performed.

  18. Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics.

    Science.gov (United States)

    Affourtit, Charles

    2016-10-01

    Skeletal muscle insulin resistance in obesity associates with mitochondrial dysfunction, but the causality of this association is controversial. This review evaluates mitochondrial models of nutrient-induced muscle insulin resistance. It transpires that all models predict that insulin resistance arises as a result of imbalanced cellular bioenergetics. The nature and precise origin of the proposed insulin-numbing molecules differ between models but all species only accumulate when metabolic fuel supply outweighs energy demand. This observation suggests that mitochondrial deficiency in muscle insulin resistance is not merely owing to intrinsic functional defects, but could instead be an adaptation to nutrient-induced changes in energy expenditure. Such adaptive effects are likely because muscle ATP supply is fully driven by energy demand. This market-economic control of myocellular bioenergetics offers a mechanism by which insulin-signalling deficiency can cause apparent mitochondrial dysfunction, as insulin resistance lowers skeletal muscle anabolism and thus dampens ATP demand and, consequently, oxidative ATP synthesis. PMID:27473535

  19. Mitochondrial DNA and Cancer Epidemiology Workshop

    Science.gov (United States)

    A workshop to review the state-of-the science in the mitochondrial DNA field and its use in cancer epidemiology, and to develop a concept for a research initiative on mitochondrial DNA and cancer epidemiology.

  20. Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction.

    Science.gov (United States)

    Finley, Lydia W S; Lee, Jaewon; Souza, Amanda; Desquiret-Dumas, Valérie; Bullock, Kevin; Rowe, Glenn C; Procaccio, Vincent; Clish, Clary B; Arany, Zoltan; Haigis, Marcia C

    2012-02-21

    Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1α is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1α activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1α (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1α is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1α is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1α is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1α nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR.

  1. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

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    Masakazu Kohda

    2016-01-01

    Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

  2. Controlled and Impaired Mitochondrial Quality in Neurons: Molecular Physiology and Prospective Pharmacology.

    Science.gov (United States)

    Matic, Ivana; Strobbe, Daniela; Frison, Michele; Campanella, Michelangelo

    2015-09-01

    Tuned mitochondrial physiology is fundamental for qualitative cellular function. This is particularly relevant for neurons, whose pathology is frequently associated with mitochondrial deficiencies. Defects in mitochondria are indeed key features in most neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). When mitochondrial coupling impairs, so does cell metabolism, trafficking and the signaling depending on the homeostasis of the mitochondrial network. Moreover, the quality control of mitochondria - via the process of mitochondrial autophagy - results biased in neurodegeneration stemming major interest on the molecular determinants of this process among neuroscientists. In this review, we highlight the most notable and acknowledged deficiencies of mitochondrial function and their relationship with diseases occurring in neurons and their transmission. The physiological aspects of mitochondrial biology in relation to bio-energy, dynamics and quality control will be discussed with the finality to form a comprehensive picture of the mitochondrial contribution to the pathophysiology of neurodegenerative syndromes. In this way we aim to set the scene to conceive novel strategies to better diagnose and target these debilitative conditions. PMID:25917207

  3. Mitochondrial proteomics on human fibroblasts for identification of metabolic imbalance and cellular stress

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    Bross Peter

    2009-05-01

    Full Text Available Abstract Background Mitochondrial proteins are central to various metabolic activities and are key regulators of apoptosis. Disturbance of mitochondrial proteins is therefore often associated with disease. Large scale protein data are required to capture the mitochondrial protein levels and mass spectrometry based proteomics is suitable for generating such data. To study the relative quantities of mitochondrial proteins in cells from cultivated human skin fibroblasts we applied a proteomic method based on nanoLC-MS/MS analysis of iTRAQ-labeled peptides. Results When fibroblast cultures were exposed to mild metabolic stress – by cultivation in galactose medium- the amount of mitochondria appeared to be maintained whereas the levels of individual proteins were altered. Proteins of respiratory chain complex I and IV were increased together with NAD+-dependent isocitrate dehydrogenase of the citric acid cycle illustrating cellular strategies to cope with altered energy metabolism. Furthermore, quantitative protein data, with a median standard error below 6%, were obtained for the following mitochondrial pathways: fatty acid oxidation, citric acid cycle, respiratory chain, antioxidant systems, amino acid metabolism, mitochondrial translation, protein quality control, mitochondrial morphology and apoptosis. Conclusion The robust analytical platform in combination with a well-defined compendium of mitochondrial proteins allowed quantification of single proteins as well as mapping of entire pathways. This enabled characterization of the interplay between metabolism and stress response in human cells exposed to mild stress.

  4. Modes of metabolic compensation during mitochondrial disease using the Drosophila model of ATP6 dysfunction.

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    Alicia M Celotto

    Full Text Available Numerous mitochondrial DNA mutations cause mitochondrial encephalomyopathy: a collection of related diseases for which there exists no effective treatment. Mitochondrial encephalomyopathies are complex multisystem diseases that exhibit a relentless progression of severity, making them both difficult to treat and study. The pathogenic and compensatory metabolic changes that are associated with chronic mitochondrial dysfunction are not well understood. The Drosophila ATP6(1 mutant models human mitochondrial encephalomyopathy and allows the study of metabolic changes and compensation that occur throughout the lifetime of an affected animal. ATP6(1animals have a nearly complete loss of ATP synthase activity and an acute bioenergetic deficit when they are asymptomatic, but surprisingly we discovered no chronic bioenergetic deficit in these animals during their symptomatic period. Our data demonstrate dynamic metabolic compensatory mechanisms that sustain normal energy availability and activity despite chronic mitochondrial complex V dysfunction resulting from an endogenous mutation in the mitochondrial DNA. ATP6(1animals compensate for their loss of oxidative phosphorylation through increases in glycolytic flux, ketogenesis and Kreb's cycle activity early during pathogenesis. However, succinate dehydrogenase activity is reduced and mitochondrial supercomplex formation is severely disrupted contributing to the pathogenesis seen in ATP6(1 animals. These studies demonstrate the dynamic nature of metabolic compensatory mechanisms and emphasize the need for time course studies in tractable animal systems to elucidate disease pathogenesis and novel therapeutic avenues.

  5. Aerobic fitness does not modulate protein metabolism in response to increased exercise: a controlled trial

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    Byerley Lauri O

    2009-06-01

    Full Text Available Abstract Background A sudden increase in exercise and energy expenditure is associated with an increase in protein turnover and nitrogen excretion. This study examined how a sudden increase in exercise-induced energy expenditure affected whole body protein metabolism and nitrogen balance in people of differing levels of aerobic fitness. We hypothesized that alterations in whole-body protein turnover would be attenuated, and nitrogen balance would be preserved, in individual with higher levels of aerobic fitness. Methods Eleven men, categorized as either having a lower (LOW-FIT; n = 5 or higher (FIT; n = 6 aerobic fitness level, completed a 4-d baseline period (BL of an energy balance diet while maintaining usual physical activity level, followed by a 7-d intervention consisting of 1,000 kcal·d-1 increased energy expenditure via exercise (50–65% VO2peak. All volunteers consumed 0.9 g protein·kg-1·d-1 and total energy intake was adjusted to maintain energy balance throughout the 11-d study. Mean nitrogen balance (NBAL was determined for BL, days 5–8 (EX1, and days 9–11 (EX2. Whole-body protein turnover was derived from phenylalanine and tyrosine kinetics assessed while fasting at rest on days 4, 7, and 12 using a priming dose of L-[ring-15N]tyrosine and a 4-h primed, continuous infusion of L-[15N]phenylalanine and L-[ring-2H4]tyrosine. Results A significant main effect of time indicated that NBAL increased over the course of the intervention; however, a group-by-time interaction was not observed. Although FIT demonstrated a lower net protein oxidation and higher net protein balance compared to LOW-FIT, neither the effect of time nor a group-by-time interaction was significant for Phe flux, net protein oxidation, or derived whole-body protein synthesis and net protein balance. Conclusion The absence of significant group-by-time interactions in protein metabolism (i.e., NBAL and whole-body protein turnover between LOW-FIT and FIT males

  6. Unexplained gastrointestinal symptoms: Think mitochondrial disease

    OpenAIRE

    Chapman, TP; Hadley, G.; Fratter, C; Cullen, SN; Bax, BE; Bain, MD; Sapsford, RA; Poulton, J; Travis, SP

    2014-01-01

    Defects in mitochondrial function are increasingly recognised as central to the pathogenesis of many diseases, both inherited and acquired. Many of these mitochondrial defects arise from abnormalities in mitochondrial DNA and can result in multisystem disease, with gastrointestinal involvement common. Moreover, mitochondrial disease may present with a range of non-specific symptoms, and thus can be easily misdiagnosed, or even considered to be non-organic.We describe the clinical, histopathol...

  7. Unexplained gastrointestinal symptoms: think mitochondrial disease.

    OpenAIRE

    Chapman, TP; Hadley, G.; Fratter, C; Cullen, SN; Bax, BE; Bain, MD; Sapsford, RA; Poulton, J; Travis, SP

    2014-01-01

    Defects in mitochondrial function are increasingly recognised as central to the pathogenesis of many diseases, both inherited and acquired. Many of these mitochondrial defects arise from abnormalities in mitochondrial DNA and can result in multisystem disease, with gastrointestinal involvement common. Moreover, mitochondrial disease may present with a range of non-specific symptoms, and thus can be easily misdiagnosed, or even considered to be non-organic. We describe the clinical, histopatho...

  8. Platelet mitochondrial membrane potential in Parkinson's disease

    OpenAIRE

    Antony, P.M.; Boyd, O.; Trefois, C.; Ammerlaan, W; Ostaszewski, M.; Baumuratov, A.S.; Longhino, L.; Antunes, L; Koopman, W.J.H.; Balling, R; Diederich, N.J.

    2014-01-01

    OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial function at the level of selected enzymatic activities in peripheral tissues have produced conflicting data. We considered the electron transport chain as a complex system with mitochondrial membrane potential as an integrative indicator for mitochondrial fitness. METHODS: Twenty-five IPD pati...

  9. Unexplained gastrointestinal symptoms: think mitochondrial disease.

    OpenAIRE

    Chapman, TP; Hadley, G.; Fratter, C; Cullen, SN; Bax, BE; Bain, MD; Sapsford, RA; Poulton, J; Travis, SP

    2014-01-01

    Defects in mitochondrial function are increasingly recognised as central to the pathogenesis of many diseases, both inherited and acquired. Many of these mitochondrial defects arise from abnormalities in mitochondrial DNA and can result in multisystem disease, with gastrointestinal involvement common. Moreover, mitochondrial disease may present with a range of non-specific symptoms, and thus can be easily misdiagnosed, or even considered to be non-organic.We describe the clinical, histopathol...

  10. Ethics of mitochondrial therapy for deafness.

    Science.gov (United States)

    Legge, Michael; Fitzgerald, Ruth P

    2014-11-07

    Mitochondrial therapy may provide the relief to many families with inherited mitochondrial diseases. However, it also has the potential for use in non-fatal disorders such as inherited mitochondrial deafness, providing an option for correction of the deafness using assisted reproductive technology. In this paper we discuss the potential for use in correcting mitochondrial deafness and consider some of the issues for the deaf community.

  11. Mitochondrial Cardiomyopathy: Pathophysiology, Diagnosis, and Management

    OpenAIRE

    Meyers, Deborah E.; Basha, Haseeb Ilias; Koenig, Mary Kay

    2013-01-01

    Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specifi...

  12. Mitochondrial myopathy and myoclonic epilepsy

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1990-03-01

    Full Text Available The authors describe a family (mother, son and two daughters with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.

  13. Enhanced aerobic nitrifying granulation by static magnetic field.

    Science.gov (United States)

    Wang, Xin-Hua; Diao, Mu-He; Yang, Ying; Shi, Yi-Jing; Gao, Ming-Ming; Wang, Shu-Guang

    2012-04-01

    One of the main challenging issues for aerobic nitrifying granules in treating high strength ammonia wastewater is the long granulation time required for activated sludge to transform into aerobic granules. The present study provides a novel strategy for enhancing aerobic nitrifying granulation by applying an intensity of 48.0mT static magnetic field. The element analysis showed that the applied magnetic field could promote the accumulation of iron compounds in the sludge. And then the aggregation of iron decreased the full granulation time from 41 to 25days by enhancing the setting properties of granules and stimulating the secretion of extracellular polymeric substances (EPS). Long-term, cycle experiments and fluorescence in-situ hybridization (FISH) analysis proved that an intensity of 48.0mT magnetic field could enhance the activities and growth of nitrite-oxidizing bacteria (NOB). These findings suggest that magnetic field is helpful and reliable for accelerating the aerobic nitrifying granulation.

  14. THE RELATIONSHIP OF CHOREOGRAPHY PREPARATION AND ARTISTRY IN AEROBIC GYMNASTICS

    Directory of Open Access Journals (Sweden)

    I. V. Sokolova

    2015-02-01

    Full Text Available Examines the impact choreography training in sports aerobics on artistic skills.Objective to investigate whether the use of funds choreo-graphy in training athletes involved in sports aerobics, to find the relationship between choreographic training and asses-sment for artistry.Method or methodology of work methods of studying the theoretical ski works of scientific content, analysis and processing of scientific texts.The results revealed the relationship between estimates for artistry and means-you dance training in sports aerobics. The scope of the results, the materials may be used by coaches in sports aerobics, for further research on the problem of constructing workout.

  15. WAYS TO IMPROVE THE PHYSICAL FITNESS THROUGH AEROBIC GYMNASTICS MEANS

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    Zaharia A.M.

    2013-07-01

    Full Text Available This research aimed to study the probable effects that aerobic gymnastics could have on the body, for improving the physical fitness. The main goal of the research was to identify the effects the aerobic gymnastics has in improving physical fitness.This research was conducted on 15 subjects between 18 and 30 years old, who participated in aerobic gymnastics fitness-type lessons, three times a week. The programs comprised exercises of physical development , stretching and elasticity, of relaxation, of coordination, and not in the least, of muscle strengthening. In order to evaluate the effectiveness of the applied means, the Ruffier test was used to assess the physical fitness of the subjects, and the Dorgo Index, to assess the cool-down response. The research data emphasized the subjects' interest for their physical fitness through a dynamic activity, constituting an argument for the practice of aerobic gymnastics throughout one's entire life, as a mean to preserve one's youth and beauty.

  16. Aerobic training and postexercise protein in facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Andersen, Grete; Prahm, Kira P; Dahlqvist, Julia R;

    2015-01-01

    OBJECTIVE: To investigate the effect of regular aerobic training and postexercise protein-carbohydrate supplementation in patients with facioscapulohumeral muscular dystrophy (FSHD). METHODS: In this randomized, double-blind, placebo-controlled parallel study, we randomized untrained men (n = 21...

  17. Tissue mitochondrial DNA changes. A stochastic system.

    Science.gov (United States)

    Kopsidas, G; Kovalenko, S A; Heffernan, D R; Yarovaya, N; Kramarova, L; Stojanovski, D; Borg, J; Islam, M M; Caragounis, A; Linnane, A W

    2000-06-01

    Several lines of evidence support the view that the bioenergetic function of the mitochondria in postmitotic tissue deteriorates during normal aging. Skeletal muscle is one such tissue that undergoes age-related fiber loss and atrophy and an age-associated rise in the number of cytochrome c oxidase (COX) deficient fibers. With such metabolic pressure placed on skeletal muscle it would be an obvious advantage to supplement the cellular requirement for energy by up-regulating glycolysis, and alternative pathway for energy synthesis. Analysis of rat skeletal muscle utilizing antibodies directed against key enzymes involved in glycolysis has provided evidence of an age-associated increase in the enzymes involved in glycolysis. Fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase protein levels appeared to increase in the soleus, gracilis, and quadriceps muscle from aged rats. The increase in the level of these proteins appeared to correlate to a corresponding decrease in the amount of cytochrome c oxidase protein measured in the same tissue. Together these results are interpreted to represent a general upregulation of glycolysis that occurs in response to the age-associated decrease in mitochondrial energy capacity. Mitochondrial DNA (mtDNA) damage and mutations may accumulate with advancing age until they reach a threshold level were they impinge on the bioenergy capacity of the cell or tissue. Evidence indicates that mtDNA from the skeletal muscle of both aged rats and humans not only undergoes changes at the nucleotide sequence level (mutations and DNA damage), but also undergoes modifications at the tertiary level to generate unique age-related conformational mtDNA species. One particular age-related conformational form was only detected in aged rat tissues with high demands on respiration, specifically in heart, kidney, soleus muscle, and, to a lesser extent, the quadriceps muscle. The age-related form was not

  18. Tissue mitochondrial DNA changes. A stochastic system.

    Science.gov (United States)

    Kopsidas, G; Kovalenko, S A; Heffernan, D R; Yarovaya, N; Kramarova, L; Stojanovski, D; Borg, J; Islam, M M; Caragounis, A; Linnane, A W

    2000-06-01

    Several lines of evidence support the view that the bioenergetic function of the mitochondria in postmitotic tissue deteriorates during normal aging. Skeletal muscle is one such tissue that undergoes age-related fiber loss and atrophy and an age-associated rise in the number of cytochrome c oxidase (COX) deficient fibers. With such metabolic pressure placed on skeletal muscle it would be an obvious advantage to supplement the cellular requirement for energy by up-regulating glycolysis, and alternative pathway for energy synthesis. Analysis of rat skeletal muscle utilizing antibodies directed against key enzymes involved in glycolysis has provided evidence of an age-associated increase in the enzymes involved in glycolysis. Fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase protein levels appeared to increase in the soleus, gracilis, and quadriceps muscle from aged rats. The increase in the level of these proteins appeared to correlate to a corresponding decrease in the amount of cytochrome c oxidase protein measured in the same tissue. Together these results are interpreted to represent a general upregulation of glycolysis that occurs in response to the age-associated decrease in mitochondrial energy capacity. Mitochondrial DNA (mtDNA) damage and mutations may accumulate with advancing age until they reach a threshold level were they impinge on the bioenergy capacity of the cell or tissue. Evidence indicates that mtDNA from the skeletal muscle of both aged rats and humans not only undergoes changes at the nucleotide sequence level (mutations and DNA damage), but also undergoes modifications at the tertiary level to generate unique age-related conformational mtDNA species. One particular age-related conformational form was only detected in aged rat tissues with high demands on respiration, specifically in heart, kidney, soleus muscle, and, to a lesser extent, the quadriceps muscle. The age-related form was not

  19. Nitrifying and denitrifying bacteria in aerobic granules formed in sequencing batch airlift reactors

    Institute of Scientific and Technical Information of China (English)

    WANG Fang; YANG Fenglin; QI Aijiu

    2007-01-01

    The purpose of this study was to investigate nitrifying bacteria and denitrifying bacteria isolated from aerobic granules.Aerobic granules were formed in an internal-circulate sequencing batch airlift reactor(SBAR)and biodegradation of NH3 -N was analyzed in the reactor.Bacteria were isolated and determined from aerobic granules using selected media.The growth properties and morphology of bacteria colonies were observed by controlling aerobic or anaerobic conditions in the culture medium.It was found that bacteria in aerobic granules were diverse and some of them were facultative aerobes.The diversity of bacteria in aerobic granules was a premise of simultaneous nitrification and denitrification.

  20. Kinetics and thermodynamics of biodegradation of hydrolyzed polyacrylamide under anaerobic and aerobic conditions.

    Science.gov (United States)

    Zhao, Lanmei; Bao, Mutai; Yan, Miao; Lu, Jinren

    2016-09-01

    Kinetics and thermodynamics of hydrolyzed polyacrylamide (HPAM) biodegradation in anaerobic and aerobic activated sludge biochemical treatment systems were explored to determine the maximum rate and feasibility of HPAM biodegradation. The optimal nutrient proportions for HPAM biodegradation were determined to be 0.08g·L(-1) C6H12O6, 1.00g·L(-1) NH4Cl, 0.36g·L(-1) NaH2PO4 and 3.00g·L(-1) K2HPO4 using response surface methodology (RSM). Based on the kinetics, the maximum HPAM biodegradation rates were 16.43385mg·L(-1)·d(-1) and 2.463mg·L(-1)·d(-1) in aerobic and anaerobic conditions, respectively. The activation energy (Ea) of the aerobic biodegradation was 48.9897kJ·mol(-1). Entropy changes (ΔS) of biochemical treatment system decreased from 216.21J·K(-1) to 2.39J·K(-1). Thermodynamic windows of opportunity for HPAM biodegradation were drawn. And it demonstrated HPAM was biodegraded into acetic acid and CO2 under laboratory conditions. Growth-process equations for functional bacteria anaerobically grown on polyacrylic acid were constructed and it confirmed electron equivalence between substrate and product. PMID:27235971

  1. Mitochondrial Stress Signalling: HTRA2 and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Enrico Desideri

    2012-01-01

    Full Text Available Mitochondria are cellular energy generators whose activity requires a continuous supply of oxygen. Recent genetic analysis has suggested that defects in mitochondrial quality control may be key factors in the development of Parkinson’s disease (PD. Mitochondria have a crucial role in supplying energy to the brain, and their deterioration can affect the function and viability of neurons, contributing to neurodegeneration. These organelles can sow the seeds of their own demise because they generate damaging oxygen-free radicals as a byproduct of their intrinsic physiological functions. Mitochondria have therefore evolved specific molecular quality control mechanisms to compensate for the action of damaging agents such as oxygen-free radicals. PTEN-induced putative kinase 1 (PINK1 and high-temperature-regulated A2 (HTRA2, a mitochondrial protease, have recently been proposed to be key modulators of mitochondrial molecular quality control. Here, we review some of the most recent advances in our understanding of mitochondria stress-control pathways, focusing on how signalling by the p38 stress kinase pathway may regulate mitochondrial stress by modulating the activity of HTRA2 via PINK1 and cyclin-dependent kinase 5 (CDK5. We also propose how defects in this pathway may contribute to PD.

  2. Mitochondrial dynamics, quality control and miRNA regulation in skeletal muscle: implications for obesity and related metabolic disease.

    Science.gov (United States)

    Dahlmans, Dennis; Houzelle, Alexandre; Schrauwen, Patrick; Hoeks, Joris

    2016-06-01

    The western dietary habits and sedentary lifestyle largely contributes to the growing epidemic of obesity. Mitochondria are at the front line of cellular energy homoeostasis and are implicated in the pathophysiology of obesity and obesity-related metabolic disease. In recent years, novel aspects in the regulation of mitochondrial metabolism, such as mitochondrial dynamics, mitochondrial protein quality control and post-transcriptional regulation of genes coding for mitochondrial proteins, have emerged. In this review, we discuss the recent findings concerning the dysregulation of these processes in skeletal muscle in obesogenic conditions. PMID:27129097

  3. p53 aerobics: the major tumor suppressor fuels your workout.

    Science.gov (United States)

    Kruse, Jan-Philipp; Gu, Wei

    2006-07-01

    In addition to its role as the central regulator of the cellular stress response, p53 can regulate aerobic respiration via the novel transcriptional target SCO2, a critical regulator of the cytochrome c oxidase complex (Matoba et al., 2006). Loss of p53 results in decreased oxygen consumption and aerobic respiration and promotes a switch to glycolysis, thereby reducing endurance during physical exercise. PMID:16814724

  4. Dosing method of physical activity in aerobics classes for students

    OpenAIRE

    Beliak Yu. I.; Zinchenko N.M.

    2014-01-01

    Purpose : reasons for the method of dosing of physical activity in aerobics classes for students. The basis of the method is the evaluation of the metabolic cost of funds used in them. Material : experiment involved the assessment of the pulse response of students to load complexes classical and step aerobics (n = 47, age 20-23 years). In complexes used various factors regulating the intensity: perform combinations of basic steps, involvement of movements with his hands, holding in hands dumb...

  5. Water aerobics in pregnancy: cardiovascular response, labor and neonatal outcomes

    OpenAIRE

    Braga Angelica F; Cecatti Jose G; Pereira Rosa I; Baciuk Erica P; Cavalcante Sergio R

    2008-01-01

    Abstract Background To evaluate the association between water aerobics, maternal cardiovascular capacity during pregnancy, labor and neonatal outcomes. Methods A randomized, controlled clinical trial was carried out in which 34 pregnant women were allocated to a water aerobics group and 37 to a control group. All women were submitted to submaximal ergometric tests on a treadmill at 19, 25 and 35 weeks of pregnancy and were followed up until delivery. Oxygen consumption (VO2 max), cardiac outp...

  6. Audio Processing Solution for Video Conference Based Aerobics

    OpenAIRE

    Berggren, Magnus; Stjernberg, Louise; Lindström, Fredric; Claesson, Ingvar

    2010-01-01

    In this paper an audio processing solution for video conference based aerobics is presented. The proposed solution leaves the workout music unaltered by separating it from the speech and processing each signal separately. The speech signal processing is also performed at a lower sample rate, which saves computational power. Real time evaluation of the system shows that high quality music as well as a good two-way communication is maintained during the aerobic session.

  7. Fetal cardiotocography before and after water aerobics during pregnancy

    OpenAIRE

    Silveira Carla; Pereira Belmiro G; Cecatti Jose G; Cavalcante Sergio R; Pereira Rosa I

    2010-01-01

    Abstract Objective To evaluate the effect of moderate aerobic physical activity in water on fetal cardiotocography patterns in sedentary pregnant women. Method In a non-randomized controlled trial, 133 previously sedentary pregnant women participated in multiple regular sessions of water aerobics in a heated swimming pool. Cardiotocography was performed for 20 minutes before and just after the oriented exercise. Cardiotocography patterns were analyzed pre- and post-exercise according to gesta...

  8. Impact of brisk walking and aerobics in overweight women

    OpenAIRE

    Melam, Ganeswara Rao; Alhusaini, Adel A.; Buragadda, Syamala; Kaur, Taranpreet; Khan, Imran Ali

    2016-01-01

    [Purpose] Lack of physical activity and an uncontrolled diet cause excessive weight gain, which leads to obesity and other metabolic disorders. Studies have indicated that brisk walking and aerobics are the best methods for controlling and reducing weight and body mass composition. [Subjects and Methods] In this study, 45 overweight women were enrolled and divided into 3 groups. Women not involved in brisk walking or aerobics were included in group A (n = 15) as control subjects; women involv...

  9. THE RELATIONSHIP OF CHOREOGRAPHY PREPARATION AND ARTISTRY IN AEROBIC GYMNASTICS

    OpenAIRE

    I. V. Sokolova

    2015-01-01

    Examines the impact choreography training in sports aerobics on artistic skills.Objective to investigate whether the use of funds choreo-graphy in training athletes involved in sports aerobics, to find the relationship between choreographic training and asses-sment for artistry.Method or methodology of work methods of studying the theoretical ski works of scientific content, analysis and processing of scientific texts.The results revealed the relationship between estimates for artistry and me...

  10. The medically important aerobic actinomycetes: epidemiology and microbiology.

    OpenAIRE

    McNeil, M. M.; Brown, J. M.

    1994-01-01

    The aerobic actinomycetes are soil-inhabiting microorganisms that occur worldwide. In 1888, Nocard first recognized the pathogenic potential of this group of microorganisms. Since then, several aerobic actinomycetes have been a major source of interest for the commercial drug industry and have proved to be extremely useful microorganisms for producing novel antimicrobial agents. They have also been well known as potential veterinary pathogens affecting many different animal species. The medic...

  11. Water Aerobics as a Form of Health Activities

    Directory of Open Access Journals (Sweden)

    Anna S. Batrak

    2013-09-01

    Full Text Available The offered literature review considers water aerobics as a form of health activities. Water aerobics is wide spread and popular, especially among women, because it is also the form of adaptive and health activities. It enlarges general physiological effect of physical exercises on the human body. Regular exercises improve physical fitness and physical development, health, mood, sleep, intensify activities and working efficiency.

  12. Maximal aerobic exercise following prolonged sleep deprivation.

    Science.gov (United States)

    Goodman, J; Radomski, M; Hart, L; Plyley, M; Shephard, R J

    1989-12-01

    The effect of 60 h without sleep upon maximal oxygen intake was examined in 12 young women, using a cycle ergometer protocol. The arousal of the subjects was maintained by requiring the performance of a sequence of cognitive tasks throughout the experimental period. Well-defined oxygen intake plateaus were obtained both before and after sleep deprivation, and no change of maximal oxygen intake was observed immediately following sleep deprivation. The endurance time for exhausting exercise also remained unchanged, as did such markers of aerobic performance as peak exercise ventilation, peak heart rate, peak respiratory gas exchange ratio, and peak blood lactate. However, as in an earlier study of sleep deprivation with male subjects (in which a decrease of treadmill maximal oxygen intake was observed), the formula of Dill and Costill (4) indicated the development of a substantial (11.6%) increase of estimated plasma volume percentage with corresponding decreases in hematocrit and red cell count. Possible factors sustaining maximal oxygen intake under the conditions of the present experiment include (1) maintained arousal of the subjects with no decrease in peak exercise ventilation or the related respiratory work and (2) use of a cycle ergometer rather than a treadmill test with possible concurrent differences in the impact of hematocrit levels and plasma volume expansion upon peak cardiac output and thus oxygen delivery to the working muscles. PMID:2628360

  13. Aerobic training in children with cerebral palsy.

    Science.gov (United States)

    Nsenga, A L; Shephard, R J; Ahmaidi, S; Ahmadi, S

    2013-06-01

    Rehabilitation is a major goal for children with cerebral palsy, although the potential to enhance cardio-respiratory fitness in such individuals remains unclear. This study thus compared current cardio-respiratory status between children with cerebral palsy and able-bodied children, and examined the ability to enhance the cardio-respiratory fitness of children with cerebral palsy by cycle ergometer training. 10 children with cerebral palsy (Gross Motor Function Classification System levels I and II) participated in thrice-weekly 30 min cycle ergometer training sessions for 8 weeks (mean age: 14.2±1.9 yrs). 10 additional subjects with cerebral palsy (mean age: 14.2±1.8 yrs) and 10 able-bodied subjects (mean age: 14.1±2.1 yrs) served as controls, undertaking no training. All subjects undertook a progressive cycle ergometer test of cardio-respiratory fitness at the beginning and end of the 8-week period. Cardio-respiratory parameters [oxygen intake V˙O2), ventilation V ˙ E) and heart rate (HR)] during testing were measured by Cosmed K4 b gas analyzer. The children with cerebral palsy who engaged in aerobic training improved their peak oxygen consumption, heart rate and ventilation significantly (pchildren with cerebral palsy can benefit significantly from cardio-respiratory training, and such training should be included in rehabilitation programs.

  14. The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, Kristin Kathleen; Uittenbogaard, Martine [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States); Chiaramello, Anne, E-mail: achiaram@gwu.edu [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)

    2012-10-15

    The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive

  15. Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock.

    Science.gov (United States)

    Muoio, Deborah M

    2014-12-01

    Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By contrast, obesity-related cardiometabolic diseases are increasingly recognized as disorders of metabolic inflexibility, in which nutrient overload and heightened substrate competition result in mitochondrial indecision, impaired fuel switching, and energy dysregulation. This Perspective offers a speculative view on the molecular origins and pathophysiological consequences of metabolic inflexibility. PMID:25480291

  16. A performance evaluation of three membrane bioreactor systems: aerobic, anaerobic, and attached-growth.

    Science.gov (United States)

    Achilli, A; Marchand, E A; Childress, A E

    2011-01-01

    Water sustainability is essential for meeting human needs for drinking water and sanitation in both developing and developed countries. Reuse, decentralization, and low energy consumption are key objectives to achieve sustainability in wastewater treatment. Consideration of these objectives has led to the development of new and tailored technologies in order to balance societal needs with the protection of natural systems. Membrane bioreactors (MBRs) are one such technology. In this investigation, a comparison of MBR performance is presented. Laboratory-scale submerged aerobic MBR (AMBR), anaerobic MBR (AnMBR), and attached-growth aerobic MBR (AtMBR) systems were evaluated for treating domestic wastewater under the same operating conditions. Long-term chemical oxygen demand (COD) and total organic carbon (TOC) monitoring showed greater than 80% removal in the three systems. The AnMBR system required three months of acclimation prior to steady operation, compared to one month for the aerobic systems. The AnMBR system exhibited a constant mixed liquor suspended solids concentration at an infinite solids retention time (i.e. no solids wasting), while the aerobic MBR systems produced approximately 0.25 g of biomass per gram of COD removed. This suggests a more economical solids management associated with the AnMBR system. Critical flux experiments were performed to evaluate fouling potential of the MBR systems. Results showed similar critical flux values between the AMBR and the AnMBR systems, while the AtMBR system showed relatively higher critical flux value. This result suggests a positive role of the attached-growth media in controlling membrane fouling in MBR systems. PMID:22049730

  17. Effect of step height on cardiorespiratory responses during aerobic step test in young Indian women

    Directory of Open Access Journals (Sweden)

    Tirthankar Chatterjee

    2013-01-01

    Full Text Available Background: Step aerobics is practiced in health centres, fitness training gyms, and academic institutions in India. This exercise module is gaining popularity day by day. But, these kind of aerobic exercise tests are less investigated for Indian women population. Objective: A widely practiced aerobic step test was applied to a group of young female to explore the effect of step height on physiological responses and suggest the best height of stepping. Method: Eight physically fit and active female university students with mean age 19.7 (±2.3 yrs, height 156.2 (±6.5 cm, weight 51.2 (±7.9 kg, and VO2max 35.7 (±4.8 ml.min-1.kg-1 volunteered for the study. Each subject performed 30 minutes of step test in two Reebok steps heights (6 inch and 8 inches with a rhythm of 120 beats.min-1. At this cadence 30 cycles of stepping up and down were completed in 1 min. Relative work load (% VO2 max, energy expenditure (EE, Heart rate (HR, percentage of age predicted maximum HR were measured using K4b2 Cosmed system. Result: The results showed that eight inch step is offering a significant higher value across most of the parameters investigated compared to six inch step. So it can be inferred that the higher the step height the higher will be the physiological responses. Conclusion: The present study clearly demonstrates that aerobic stepping on 6 inch bench height for 30 minutes with a cadence of 120 beats. min-1 may be more suitable and safe exercise module to improve cardio respiratory fitness for Indian young females. Further investigations are required to identify suitable exercise modules in terms of bench height, cadence and duration for different age groups and according to their fitness level (trained/untrained and height on larger sample size.

  18. The effect of aerobic exposure on nutritive value and fermentation parameters of maize silage

    Directory of Open Access Journals (Sweden)

    Marián MAJLÁT

    2016-06-01

    Full Text Available The objective of the study was to investigate the effect of 24 hours aerobic exposure on the nutritive value and fermentation parameters of maize silage under operating conditions in autumn. The maize silage was treated with the addition of granulated biological silage additive (Lactobacillus plantarum, Lactobacillus buchneri and Pediococcus pentosaceus in a 0.25 kg*t-1 dose of matter. The maize silage was stored in unsheltered, impassable 36x23x6m silo, covered with thin translucent underlying sheet and black upper sheet with tires laid on the top at the University farm, Ltd. Kolíňany – large scale dairy farm Oponice. Sampling of the silage from silo was realized by block cutter on 5th of October 2011 at 4 a.m. (before feeding and subsequently, maize silage was stored at the feeding table in dairy cow's stall. The sampling of the maize silage happened immediately after collection (H0 and after 24 hours of storage at the feeding table (H24. The air temperature in dairy cow's stall was 13.5 °C (H0 and after 24 hours of storage (H24 15 °C. The temperature of the silage in 30cm depth was 28 °C (H0 and 40.3 °C (H24. After 24 hours of aerobic exposure, the content of dry matter, starch, hemicelluloses and neutral detergent fiber in maize silage was statistically significantly (P < 0.05 increased. Our results indicate a reduction in vitro organic matter digestibility and a decrease in energy and nitrogen values during aerobic exposure. We found statistically significant (P < 0.05 decrease in lactic acid content, the degree of proteolysis and an increase in acetic acid (by 41% in maize silage with Lactobacillus plantarum, Lactobacillus buchneri and Pediococcus pentosaceus during 24 hours aerobic exposure.

  19. Mitochondrial disease patients' perception of dietary supplements' use.

    Science.gov (United States)

    Karaa, Amel; Kriger, Joshua; Grier, Johnston; Holbert, Amy; Thompson, John L P; Parikh, Sumit; Hirano, Michio

    2016-09-01

    Surveys of mitochondrial disease physicians conducted through the Mitochondrial Medicine Society have shown that virtually all providers recommend a variety of dietary supplements as treatments to their patients in an effort to enhance energy production and reduce oxidative stress. In this survey, we asked patients and their parents about their experiences taking these dietary supplements for mitochondrial disease. The survey was disseminated through the North American Mitochondrial Disease Consortium (NAMDC) and the Rare Disease Clinical Research Network (RDCRN) registries and gathered 162 responses. The study ascertained each patient's mitochondrial disease diagnosis, dietary supplements used, adjunct therapy, and effects of the supplements on symptoms and health. Regardless of the specific underlying mitochondrial disease, the majority of the survey respondents stated they are or have been on dietary supplements. Most patients take more than four supplements primarily coenzyme Q10, l-carnitine, and riboflavin. The majority of patients taking supplements reported health benefits from the supplements. The onset of perceived benefits was between 2weeks to 3months of initiating intake. Supplements seem to be safe, with only 28% of patients experiencing mild side-effects and only 5.6% discontinuing their intake due to intolerance. Only 9% of patients had insurance coverage for their supplements and when paying out of pocket, 95% of them spend up to $500/month. Despite the use of concomitant therapies (prescribed medications, physical therapy, diet changes and other), 45.5% of patients think that dietary supplements are the only intervention improving their symptoms. Some limitations of this study include the retrospective collection of data probably associated with substantial recall bias, lack of longitudinal follow up to document pre- and post-supplement clinical status and second hand reports by parents for children which may reflect parents' subjective

  20. Mitochondrial disease patients' perception of dietary supplements' use.

    Science.gov (United States)

    Karaa, Amel; Kriger, Joshua; Grier, Johnston; Holbert, Amy; Thompson, John L P; Parikh, Sumit; Hirano, Michio

    2016-09-01

    Surveys of mitochondrial disease physicians conducted through the Mitochondrial Medicine Society have shown that virtually all providers recommend a variety of dietary supplements as treatments to their patients in an effort to enhance energy production and reduce oxidative stress. In this survey, we asked patients and their parents about their experiences taking these dietary supplements for mitochondrial disease. The survey was disseminated through the North American Mitochondrial Disease Consortium (NAMDC) and the Rare Disease Clinical Research Network (RDCRN) registries and gathered 162 responses. The study ascertained each patient's mitochondrial disease diagnosis, dietary supplements used, adjunct therapy, and effects of the supplements on symptoms and health. Regardless of the specific underlying mitochondrial disease, the majority of the survey respondents stated they are or have been on dietary supplements. Most patients take more than four supplements primarily coenzyme Q10, l-carnitine, and riboflavin. The majority of patients taking supplements reported health benefits from the supplements. The onset of perceived benefits was between 2weeks to 3months of initiating intake. Supplements seem to be safe, with only 28% of patients experiencing mild side-effects and only 5.6% discontinuing their intake due to intolerance. Only 9% of patients had insurance coverage for their supplements and when paying out of pocket, 95% of them spend up to $500/month. Despite the use of concomitant therapies (prescribed medications, physical therapy, diet changes and other), 45.5% of patients think that dietary supplements are the only intervention improving their symptoms. Some limitations of this study include the retrospective collection of data probably associated with substantial recall bias, lack of longitudinal follow up to document pre- and post-supplement clinical status and second hand reports by parents for children which may reflect parents' subjective

  1. Polybrominated diphenyl ether congener (BDE-100) induces mitochondrial impairment.

    Science.gov (United States)

    Pereira, Lílian Cristina; de Souza, Alecsandra Oliveira; Dorta, Daniel Junqueira

    2013-06-01

    Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 μM to 50 μM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100. PMID:23302053

  2. Polybrominated diphenyl ether congener (BDE-100) induces mitochondrial impairment.

    Science.gov (United States)

    Pereira, Lílian Cristina; de Souza, Alecsandra Oliveira; Dorta, Daniel Junqueira

    2013-06-01

    Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 μM to 50 μM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100.

  3. Xanthohumol induces generation of reactive oxygen species and triggers apoptosis through inhibition of mitochondrial electron transfer chain complex I.

    Science.gov (United States)

    Zhang, Bo; Chu, Wei; Wei, Peng; Liu, Ying; Wei, Taotao

    2015-12-01

    Xanthohumol is a prenylflavonoid extracted from hops (Humulus lupulus). It possesses anti-cancer and anti-inflammatory activities in vitro and in vivo, and offers therapeutic benefits for treatment of metabolic syndromes. However, the precise mechanisms underlying its pharmacological effects remain to be elucidated, together with its cellular target. Here, we provide evidence that xanthohumol directly interacts with the mitochondrial electron transfer chain complex I (NADH dehydrogenase), inhibits the oxidative phosphorylation, triggers the production of reactive oxygen species, and induces apoptosis. In addition, we show that as a result of the inhibition of the mitochondrial oxidative phosphorylation, xanthohumol exposure causes a rapid decrease of mitochondrial transmembrane potential. Furthermore, we showed that xanthohumol up-regulates the glycolytic capacity in cells, and thus compensates cellular ATP generation. Dissection of the multiple steps of aerobic respiration by extracellular flux assays revealed that xanthohumol specifically inhibits the activity of mitochondrial complex I, but had little effect on that of complex II, III and IV. Inhibition of complex I by xanthohumol caused the overproduction of reactive oxygen species, which are responsible for the induction of apoptosis in cancer cells. We also found that isoxanthohumol, the structural isomer of xanthohumol, is inactive to cells, suggesting that the reactive 2-hydroxyl group of xanthohumol is crucial for its targeting to the mitochondrial complex I. Together, the remodeling of cell metabolism revealed here has therapeutic potential for the use of xanthohumol.

  4. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Eugenia Trushina

    Full Text Available BACKGROUND: The identification of early mechanisms underlying Alzheimer's Disease (AD and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD mutations on mitochondrial function, dynamics, and brain energetics. METHODS AND FINDINGS: We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L and the double mutation of human amyloid precursor protein APP(Tg2576 and PS1(M146L contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. CONCLUSIONS: Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy

  5. The Training Effects of Dance Aerobics: A Review with an Emphasis on the Perspectives of Investigations

    OpenAIRE

    Zaletel, Petra; Gabrilo, Goran; Perić, Mia

    2013-01-01

    The training effects of contemporary aerobics programmes (hi lo, dance aerobics, step aerobics, aqua aerobics etc.) have been frequently investigated. However, we found no recent paper which reviewed aerobic programmes with regard to their training effectiveness, characteristics of the subjects involved, variables of interest and experimental design. In this paper we summarise the findings of more than 40 studies published in the 2000–2011 period that investigated the training effects of diff...

  6. Transcutaneous application of carbon dioxide (CO2 induces mitochondrial apoptosis in human malignant fibrous histiocytoma in vivo.

    Directory of Open Access Journals (Sweden)

    Yasuo Onishi

    Full Text Available Mitochondria play an essential role in cellular energy metabolism and apoptosis. Previous studies have demonstrated that decreased mitochondrial biogenesis is associated with cancer progression. In mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α regulates the activities of multiple nuclear receptors and transcription factors involved in mitochondrial proliferation. Previously, we showed that overexpression of PGC-1α leads to mitochondrial proliferation and induces apoptosis in human malignant fibrous histiocytoma (MFH cells in vitro. We also demonstrated that transcutaneous application of carbon dioxide (CO(2 to rat skeletal muscle induces PGC-1α expression and causes an increase in mitochondrial proliferation. In this study, we utilized a murine model of human MFH to determine the effect of transcutaneous CO(2 exposure on PGC-1α expression, mitochondrial proliferation and cellular apoptosis. PGC-1α expression was evaluated by quantitative real-time PCR, while mitochondrial proliferation was assessed by immunofluorescence staining and the relative copy number of mitochondrial DNA (mtDNA was assessed by real-time PCR. Immunofluorescence staining and DNA fragmentation assays were used to examine mitochondrial apoptosis. We also evaluated the expression of mitochondrial apoptosis related proteins, such as caspases, cytochorome c and Bax, by immunoblot analysis. We show that transcutaneous application of CO(2 induces PGC-1α expression, and increases mitochondrial proliferation and apoptosis of tumor cells, significantly reducing tumor volume. Proteins involved in the mitochondrial apoptotic cascade, including caspase 3 and caspase 9, were elevated in CO(2 treated tumors compared to control. We also observed an enrichment of cytochrome c in the cytoplasmic fraction and Bax protein in the mitochondrial fraction of CO(2 treated tumors, highlighting the involvement of mitochondria in apoptosis

  7. Natural Compounds Modulating Mitochondrial Functions

    Directory of Open Access Journals (Sweden)

    Lara Gibellini

    2015-01-01

    Full Text Available Mitochondria are organelles responsible for several crucial cell functions, including respiration, oxidative phosphorylation, and regulation of apoptosis; they are also the main intracellular source of reactive oxygen species (ROS. In the last years, a particular interest has been devoted to studying the effects on mitochondria of natural compounds of vegetal origin, quercetin (Qu, resveratrol (RSV, and curcumin (Cur being the most studied molecules. All these natural compounds modulate mitochondrial functions by inhibiting organelle enzymes or metabolic pathways (such as oxidative phosphorylation, by altering the production of mitochondrial ROS and by modulating the activity of transcription factors which regulate the expression of mitochondrial proteins. While Qu displays both pro- and antioxidant activities, RSV and Cur are strong antioxidant, as they efficiently scavenge mitochondrial ROS and upregulate antioxidant transcriptional programmes in cells. All the three compounds display a proapoptotic activity, mediated by the capability to directly cause the release of cytochrome c from mitochondria or indirectly by upregulating the expression of proapoptotic proteins of Bcl-2 family and downregulating antiapoptotic proteins. Interestingly, these effects are particularly evident on proliferating cancer cells and can have important therapeutic implications.

  8. Historical Perspective on Mitochondrial Medicine

    Science.gov (United States)

    DiMauro, Salvatore; Garone, Caterina

    2010-01-01

    In this review, we trace the origins and follow the development of mitochondrial medicine from the premolecular era (1962-1988) based on clinical clues, muscle morphology, and biochemistry into the molecular era that started in 1988 and is still advancing at a brisk pace. We have tried to stress conceptual advances, such as endosymbiosis,…

  9. Coenzyme Q and Mitochondrial Disease

    Science.gov (United States)

    Quinzii, Catarina M.; Hirano, Michio

    2010-01-01

    Coenzyme Q[subscript 10] (CoQ[subscript 10]) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ[subscript 10] is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ[subscript…

  10. Mitochondrial dysfunction and Huntington disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.

  11. Supplementary Low-Intensity Aerobic Training Improves Aerobic Capacity and Does Not Affect Psychomotor Performance in Professional Female Ballet Dancers

    OpenAIRE

    Smol, Ewelina; Fredyk, Artur

    2012-01-01

    We investigated whether 6-week low-intensity aerobic training program used as a supplement to regular dance practice might improve both the aerobic capacity and psychomotor performance in female ballet dancers. To assess their maximal oxygen uptake (VO2max) and anaerobic threshold (AT), the dancers performed a standard graded bicycle ergometer exercise test until volitional exhaustion prior to and after the supplementary training. At both these occasions, the psychomotor performance (assessed...

  12. Cadmium exposure affects mitochondrial bioenergetics and gene expression of key mitochondrial proteins in the eastern oyster Crassostrea virginica Gmelin (Bivalvia: Ostreidae)

    Energy Technology Data Exchange (ETDEWEB)

    Sokolova, Inna M. [Biology Department, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States)]. E-mail: insokolo@uncc.edu; Sokolov, Eugene P. [Biology Department, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States); Ponnappa, Kavita M. [Biology Department, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States)

    2005-07-01

    Cadmium is a ubiquitous and extremely toxic metal, which strongly affects mitochondrial function of aquatic organisms in vitro; however, nothing is known about the in vivo effects of sublethal concentrations of this metal on mitochondrial bioenergetics. We have studied the effects of exposure to 0 (control) or 25 {mu}g L{sup -1} (Cd-exposed) Cd{sup 2+} on mitochondrial function and gene expression of key mitochondrial proteins in the eastern oyster Crassostrea virginica. Cadmium exposure in vivo resulted in considerable accumulation of cadmium in oyster mitochondria and in a significant decrease of ADP-stimulated respiration (state 3) by 30% indicating impaired capacity for ATP production. The decrease in state 3 respiration was similar to the level of inhibition expected from the direct effects of cadmium accumulated in oyster mitochondria. On the other hand, while no effect on proton leak was expected based on the mitochondrial accumulation of cadmium, Cd-exposed oysters in fact showed a significant decline of the proton leak rate (state 4 + respiration) by 40%. This suggested a downregulation of proton leak, which correlated with a decrease in mRNA expression of a mitochondrial uncoupling protein UCP6 and two other potential uncouplers, mitochondrial substrate carriers MSC-1 and MSC-2. Expression of other key mitochondrial proteins including cytochrome c oxidase, adenine nucleotide transporter and voltage dependent anion channel was not affected by cadmium exposure. Adenylate energy charge (AEC) was significantly lower in Cd-exposed oysters; however, this was due to higher steady state ADP levels and not to the decrease in tissue ATP levels. Our data show that adjustment of the proton leak in cadmium-exposed oysters may be a compensatory mechanism, which allows them to maintain normal mitochondrial coupling and ATP levels despite the cadmium-induced inhibition of capacity for ATP production.

  13. Formation and functions of aerobic microbial granula; Entstehung und Funktionen aerober mikrobieller Granula

    Energy Technology Data Exchange (ETDEWEB)

    Etterer, T.; Wilderer, P.A. [Technische Univ. Muenchen, Garching (Germany). Lehrstuhl und Pruefamt fuer Wasserguete- und Abfallwirtschaft

    1999-07-01

    The present project investigates the phenomenon of the formation of aerobic microbial granula and their properties. To generate granula, sequencing batch reactors fed in batches were used. As shown by microbiological assays, fungi played an above-average role in granula formation and build-up. In first degradation experiments, furthermore, chemical oxygen demand (COD) could be reduced by over 90 %. The determination yielded comparable values to activated sludge, standing on average at 1.044g/ml. (orig.) [German] Im Rahmen des hier vorgestellten Projekts wurde das Phaenomen der Bildung aerober mikrobieller Granula sowie deren Eigenschaften untersucht. Zur Erzeugung von Granula wurden schubweise beschickte Reaktoren, sogenannte Sequencing-Batch-Reaktoren (SBR) verwendet. Wie mikrobiologische Untersuchungen zeigten spielen Pilze bei der Entstehung und beim Aufbau eine ueberdurchschnittliche Rolle. Des weiteren konnte in ersten Abbauversuchen der chemische Sauerstoff-Bedarf (CSB) um ueber 90% gesenkt werden. Die Dichtebestimmung ergab vergleichbare Werte zu Belebtschlamm und zwar im Durchschnitt 1,044 g/ml. (orig.)

  14. Cyanate as energy source for nitrifiers

    OpenAIRE

    Palatinszky, Marton; Herbold, Craig; Jehmlich, Nico; Pogoda, Mario; Han, Ping; von Bergen, Martin; Lagkouvardos, Ilias; Karst, Søren M.; Galushko, Alexander; Koch, Hanna; BERRY, David; Daims, Holger; Wagner, Michael

    2015-01-01

    Ammonia- and nitrite-oxidizers are collectively responsible for the aerobic oxidation of ammonia via nitrite to nitrate and play essential roles for the global biogeochemical nitrogen cycle. The physiology of these nitrifying microbes has been intensively studied since the first experiments of Sergei Winogradsky more than a century ago. Urea and ammonia are the only recognized energy sources that promote the aerobic growth of ammonia-oxidizing bacteria and archaea. Here we report the aerobic ...

  15. [Mitochondrial quality control: the target for exercise to promote health and prevent disease].

    Science.gov (United States)

    Zhao, Yun-Gang; Li, Can; Ding, Shu-Zhe; Zhang, Yong

    2014-10-01

    Regular exercise has been known to have many benefits, for example, improving physical performance, promoting health and preventing chronic diseases such as metabolic diseases. As a very important organelles in eukaryotic cells, mitochondria exhibit superb plasticity in response to exercise. Exercise may promote mitochondrial biogenesis and eliminate the dysfunctional mitochondria via mitophagy in order to maintain the normal function of the mitochondrial network. These dynamic changes keep mitochondria in health state and ensure the energy supply for cells. This review summarized the studies on the regulation of mitochondrial quality control by exercise, and provided a reasonable explanation for exercise to promote health and prevent diseases. PMID:25764790

  16. Enhanced selection of micro-aerobic pentachlorophenol degrading granular sludge

    International Nuclear Information System (INIS)

    Graphical abstract: In this work, an aerobic column reactor was placed before the USB to maintain micro-oxygen condition in the reactor and the micro-aerobic pentachlorophenol (PCP) degrading granular sludge under oxygen-limited conditions (0.1–0.2 mg L−1) was successfully obtained. PCP degradation by the micro-aerobic system was studied and the variance of microbial community was also discussed by using PCR-DGGE analysis. - Highlights: • Micro-aerobic granular sludge was cultivated in column-type combined reactors. • PCP biodegradation, VFA accumulation and biogas production were studied. • The function of Methanogenic archaeon in the system was investigated. • Fluctuation and diversity of microbial community were discussed by DGGE analysis. • The dominated microorganisms were identified by 16S rDNA sequences. - Abstract: Column-type combined reactors were designed to cultivate micro-aerobic pentachlorophenol (PCP) degrading granular sludge under oxygen-limited conditions (0.1–0.2 mg L−1) over 39-day experimental period. Micro-aerobic granular had both anaerobic activity (SMA: 2.34 mMCH4/h g VSS) and aerobic activity (SOUR: 2.21 mMO2/h g VSS). Metabolite analysis results revealed that PCP was sequentially dechlorinated to TCP, DCP, and eventually to MCP. Methanogens were not directly involved in the dechlorination of PCP, but might played a vital role in stabilizing the overall structure of the granule sludge. For Eubacteria, the Shannon Index (2.09 in inoculated granular sludge) increased both in micro-aerobic granular sludge (2.61) and PCP-degradation granular sludge (2.55). However, for Archaea, it decreased from 2.53 to 1.85 and 1.84, respectively. Although the Shannon Index demonstrated slight difference between micro-aerobic granular sludge and PCP-degradation granular sludge, the Principal Component Analysis (PCA) indicated obvious variance of the microbial composition, revealing significant effect of micro-aerobic condition and PCP on

  17. Enhanced selection of micro-aerobic pentachlorophenol degrading granular sludge

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Yuancai, E-mail: donkey1204@hotmail.com [State Key Laboratory of Pulp and Paper Engineering, College of Light Industry and Food Science, South China University of Technology, Guangzhou 510640 (China); Chen, Yuancai, E-mail: chenyc@scut.edu.cn [State Key Laboratory of Pulp and Paper Engineering, College of Light Industry and Food Science, South China University of Technology, Guangzhou 510640 (China); Ministry of Education Key Laboratory of Pollution Control and Ecological Remediation for Industrial Agglomeration Area, College of Environment and Energy, South China University of Technology, Guangzhou 510006 (China); Song, Wenzhe, E-mail: songwenzhe007@126.com [Ministry of Education Key Laboratory of Pollution Control and Ecological Remediation for Industrial Agglomeration Area, College of Environment and Energy, South China University of Technology, Guangzhou 510006 (China); Hu, Yongyou, E-mail: ppyyhu@scut.edu.cn [State Key Laboratory of Pulp and Paper Engineering, College of Light Industry and Food Science, South China University of Technology, Guangzhou 510640 (China); Ministry of Education Key Laboratory of Pollution Control and Ecological Remediation for Industrial Agglomeration Area, College of Environment and Energy, South China University of Technology, Guangzhou 510006 (China)

    2014-09-15

    Graphical abstract: In this work, an aerobic column reactor was placed before the USB to maintain micro-oxygen condition in the reactor and the micro-aerobic pentachlorophenol (PCP) degrading granular sludge under oxygen-limited conditions (0.1–0.2 mg L{sup −1}) was successfully obtained. PCP degradation by the micro-aerobic system was studied and the variance of microbial community was also discussed by using PCR-DGGE analysis. - Highlights: • Micro-aerobic granular sludge was cultivated in column-type combined reactors. • PCP biodegradation, VFA accumulation and biogas production were studied. • The function of Methanogenic archaeon in the system was investigated. • Fluctuation and diversity of microbial community were discussed by DGGE analysis. • The dominated microorganisms were identified by 16S rDNA sequences. - Abstract: Column-type combined reactors were designed to cultivate micro-aerobic pentachlorophenol (PCP) degrading granular sludge under oxygen-limited conditions (0.1–0.2 mg L{sup −1}) over 39-day experimental period. Micro-aerobic granular had both anaerobic activity (SMA: 2.34 mMCH{sub 4}/h g VSS) and aerobic activity (SOUR: 2.21 mMO{sub 2}/h g VSS). Metabolite analysis results revealed that PCP was sequentially dechlorinated to TCP, DCP, and eventually to MCP. Methanogens were not directly involved in the dechlorination of PCP, but might played a vital role in stabilizing the overall structure of the granule sludge. For Eubacteria, the Shannon Index (2.09 in inoculated granular sludge) increased both in micro-aerobic granular sludge (2.61) and PCP-degradation granular sludge (2.55). However, for Archaea, it decreased from 2.53 to 1.85 and 1.84, respectively. Although the Shannon Index demonstrated slight difference between micro-aerobic granular sludge and PCP-degradation granular sludge, the Principal Component Analysis (PCA) indicated obvious variance of the microbial composition, revealing significant effect of micro-aerobic

  18. Mitochondrial rejuvenation after induced pluripotency.

    Directory of Open Access Journals (Sweden)

    Steven T Suhr

    Full Text Available BACKGROUND: As stem cells of the early embryo mature and differentiate into all tissues, the mitochondrial complement undergoes dramatic functional improvement. Mitochondrial activity is low to minimize generation of DNA-damaging reactive oxygen species during pre-implantation development and increases following implantation and differentiation to meet higher metabolic demands. It has recently been reported that when the stem cell type known as induced pluripotent stem cells (IPSCs are re-differentiated for several weeks in vitro, the mitochondrial complement progressively re-acquires properties approximating input fibroblasts, suggesting that despite the observation that IPSC conversion "resets" some parameters of cellular aging such as telomere length, it may have little impact on other age-affected cellular systems such as mitochondria in IPSC-derived cells. METHODOLOGY/PRINCIPAL FINDINGS: We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1 that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2 the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturation found in a developing mammal. CONCLUSIONS/SIGNIFICANCE: These results - coupled with earlier data from our laboratory - suggest that IPSC conversion not only resets the "biological clock", but can also rejuvenate the energetic capacity of derived cells.

  19. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    Science.gov (United States)

    Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A

    2016-09-01

    Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function.

  20. Partitioning of Respiration in an Animal-Algal Symbiosis: Implications for Different Aerobic Capacity Between Symbiodinium spp.

    Directory of Open Access Journals (Sweden)

    Thomas David Hawkins

    2016-04-01

    Full Text Available Cnidarian-dinoflagellate symbioses are ecologically important and the subject of much investigation. However, our understanding of critical aspects of symbiosis physiology, such as the partitioning of total respiration between the host and symbiont, remains incomplete. Specifically, we know little about how the relationship between host and symbiont respiration varies between different holobionts (host-symbiont combinations. We applied molecular and biochemical techniques to investigate aerobic respiratory capacity in naturally symbiotic Exaiptasia pallida sea anemones, alongside animals infected with either homologous ITS2-type A4 Symbiodinium or a heterologous isolate of Symbiodinium minutum (ITS2-type B1. In naturally symbiotic anemones, host, symbiont, and total holobiont mitochondrial citrate synthase (CS enzyme activity, but not host mitochondrial copy number, were reliable predictors of holobiont respiration. There was a positive association between symbiont density and host CS specific activity (mg protein-1, and a negative correlation between host- and symbiont CS specific activities. Notably, partitioning of total CS activity between host and symbiont in this natural E. pallida population was significantly different to the host/symbiont biomass ratio. In re-infected anemones, we found significant between-holobiont differences in the CS specific activity of the algal symbionts. Furthermore, the relationship between the partitioning of total CS activity and the host/symbiont biomass ratio differed between holobionts. These data have broad implications for our understanding of cnidarian-algal symbiosis. Specifically, the long-held assumption of equivalency between symbiont/host biomass and respiration ratios can result in significant overestimation of symbiont respiration and potentially erroneous conclusions regarding the percentage of carbon translocated to the host. The interspecific variability in symbiont aerobic capacity provides