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PubMed1997

Detection of early ischemic damage by analysis of mitochondrial function in skinned fibers.

The skinned fibers technique was applied for studies of the effects of global acute ischemia (1 h at 37 degrees C) and long time (15 h) hypothermic (4 degrees C) preservation of isolated rat hearts under different conditions (immersion or low-flow perfusion) on mitochondrial function in the cells in vivo. Skinned fibers were obtained by using saponin for permeabilization of the sarcolemma in separated fiber bundles cut from left ventricle. The experimental protocol of the respiration rate determination included a cytochrome c test to check the intactness of the outer mitochondrial membrane. The apparent K(m) for ADP and the effect of creatine on the mitochondrial activity were also evaluated in these permeabilized fibers, taken from different groups of hearts. The preservation of low-flow perfused hearts resulted only in a slight decrease of creatine (20 mM) stimulated respiration at 0.1 mM ADP. The fibers from ischemic hearts or from hearts preserved by immersion showed a decrease of the apparent K(m) for ADP, and a complete loss of the stimulatory effect of creatine. In these fibers, we could observe that the outer mitochondrial membrane was damaged. In conclusion, the results of this study show that assessment of mitochondrial parameters sensitive to organelles swelling--intactness of outer membrane and functionally coupled creatine kinase reaction--are the most sensitive indicators of early hypoxic or ischemic damage to mitochondria. Their determination in biopsy samples could be used for evaluation of the efficiency of the cardiac protection in heart surgery.

Adenosine Diphosphate↗

PubMed2005

Mitochondrial function in Leydig cell steroidogenesis.

The first and rate-limiting step in the biosynthesis of steroid hormones is the transfer of cholesterol into mitochondria, which is facilitated by the steroidogenic acute regulatory (StAR) protein. Recent studies of Leydig cell function have focused on the molecular events controlling steroidogenesis; however, few studies have examined the importance of the mitochondria. The purpose of this investigation was to determine which aspects of mitochondrial function are necessary for Leydig cell steroidogenesis. MA-10 tumor Leydig cells were treated with 8-bromo-cAMP (cAMP) and site-specific mitochondrial disrupters, pro-oxidants, and their effects on progesterone synthesis, StAR expression, mitochondrial membrane potential (delta psi(m)) and ATP synthesis were determined. Dissipating delta psi(m) with CCCP inhibited progesterone synthesis, even in the presence of newly synthesized StAR protein. The electron transport inhibitor antimycin A significantly reduced cellular ATP, inhibited steroidogenesis, and reduced StAR protein expression. The F0/F1 ATPase inhibitor oligomycin reduced cellular ATP and inhibited progesterone synthesis and StAR protein expression, but had no effect on delta psi(m). Disruption of pH with nigericin significantly reduced progesterone production and StAR protein, but had minimal effects on delta psi(m). Sodium arsenite at low concentrations inhibited StAR protein but not mRNA expression and inhibited progesterone without disrupting delta psi(m). The mitochondrial Ca2+ inhibitor Ru360 also inhibited StAR protein expression. These results demonstrate that delta psi(m), ATP synthesis, delta pH and [Ca2+]mt are all required for steroid biosynthesis, and that mitochondria are sensitive to oxidative stress. These results suggest that mitochondria must be energized, polarized, and actively respiring to support Leydig cell steroidogenesis and alterations in the state of mitochondria may be involved in regulating steroid biosynthesis.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2006

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

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.

Acclimatization↗

PubMed2006

Effects of dietary genistein on hepatic lipid metabolism and mitochondrial function in mice fed high-fat diets.

OBJECTIVE: Genistein has been suggested to prevent insulin resistance and its related diseases. We investigated the effects of dietary genistein at different levels on hepatic lipid levels and mitochondrial functions in mice fed high-fat diets. METHODS: C57BL/6J mice were randomly divided into four groups and fed a high-fat diet containing genistein at levels of 0%, 0.1%, 0.2%, and 0.4% (HF, HF + 0.1G, HF + 0.2G, and HF + 0.4G) for 12 wk. We measured lipid levels in the blood and liver. We also observed messenger RNA (mRNA) expression of genes encoding proteins related to lipid and energy metabolism and antioxidant defense system and mitochondrial enzyme activities in the liver. RESULTS: The induction of fatty liver by HF was substantially decreased in the HF + 0.2G and HF + 0.4G groups. Peroxisome proliferator-activated receptorgamma coactivator mRNA was increased by HF + 0.4G. Although genistein did not affect peroxisomal acyl-CoA oxidase mRNA expression, it increased medium-chain acyl-CoA dehydrogenase mRNA expression in a dose-dependent manner and HF + 0.2G increased uncoupling protein-2 mRNA expression two-fold relative to HF mice. Genistein decreased malondialdehyde levels and increased glutathione levels in liver homogenates, regardless of dose. The HF + 0.1G diet increased mitochondrial glutathione peroxidase activity and mitochondrial succinate dehydrogenase activity. CONCLUSIONS: Although genistein at higher levels decreased hepatic fat accumulation possibly by increasing fatty acid oxidation and uncoupling protein, low-dose genistein increased mitochondrial enzyme activities in mice with fatty liver and obesity induced by high-fat diets.

Acyl-CoA Dehydrogenase↗

PubMed2002

Alteration of mitochondrial function in a model of chronic ischemia in vivo in rat heart.

The aim of this study was to investigate mitochondrial alterations in an animal model of chronic myocardial ischemia in rats obtained by surgical constriction of the left coronary artery. Resting coronary blood flow was measured using the fluorescent microsphere technique. Contractile function, defined by rate-pressure product, and myocardial oxygen consumption were measured in a Langendorff preparation. The mitochondrial function was evaluated on permeabilized skinned fibers. Three weeks after surgery, ischemic hearts showed a significant decrease in coronary blood flow compared with sham. Hemodynamic measurements showed a significant systolic and diastolic dysfunction. Alterations in mitochondrial function in ischemic hearts were mainly characterized by a significant decrease in the maximal velocity and apparent half-saturation constant for ADP, loss of the stimulatory effect of creatine, and a stimulatory effect of exogenous cytochrome c. These functional alterations were supported by structural alterations characterized by mitochondrial clustering and swelling associated with membrane rupture. We conclude that the alterations in systolic function after chronic ischemia are supported by severe modifications of mitochondrial structure and function.

Adenosine Diphosphate↗

PubMed2003

Tomato EF-Ts(mt), a functional mitochondrial translation elongation factor from higher plants.

Ethylene-induced ripening in tomato (Lycopersicon esculentum) resulted in the accumulation of a transcript designated LeEF-Ts(mt) that encodes a protein with significant homology to bacterial Ts translational elongation factor (EF-Ts). Transient expression in tobacco and sunflower protoplasts of full-length and truncated LeEF-Ts(mt)-GFP fusion constructs and confocal microscopy observations clearly demonstrated the targeting of LeEF-Ts(mt) to mitochondria and not to chloroplasts and the requirement for a signal peptide for the proper sorting of the protein. Escherichia coli recombinant LeEF-Ts(mt) co-eluted from Ni-NTA resins with a protein corresponding to the molecular weight of the elongation factor EF-Tu of E. coli, indicating an interaction with bacterial EF-Tu. Increasing the GDP concentration in the extraction buffer reduced the amount of EF-Tu in the purified LeEF-Ts(mt) fraction. The purified LeEF-Ts(mt) stimulated the poly(U)-directed polymerization of phenylalanine 10-fold in the presence of EF-Tu. Furthermore, LeEF-Ts(mt) was capable of catalysing the nucleotide exchange reaction with E. coli EF-Tu. Altogether, these data demonstrate that LeEF-Ts(mt) encodes a functional mitochondrial EF-Ts. LeEF-Ts(mt) represents the first mitochondrial elongation factor to be isolated and functionally characterized in higher plants.

Amino Acid Sequence↗

PubMed2004

Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions.

The effects of gold(I) complexes (auranofin, triethylphosphine gold and aurothiomalate), gold(III) complexes ([Au(2,2'-diethylendiamine)Cl]Cl(2), [(Au(2-(1,1-dimethylbenzyl)-pyridine) (CH(3)COO)(2)], [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)(OH)](PF(6)), [Au(bipy(dmb)-H)(2,6-xylidine)](PF(6))), metal ions (zinc and cadmium acetate) and metal complexes (cisplatin, zinc pyrithione and tributyltin) on mitochondrial thioredoxin reductase and mitochondrial functions have been examined. Both gold(I) and gold(III) complexes are extremely efficient inhibitors of thioredoxin reductase showing IC(50) ranging from 0.020 to 1.42 microM while metal ions and complexes not containing gold are less effective, exhibiting IC(50) going from 11.8 to 76.0 microM. At variance with thioredoxin reductase, auranofin is completely ineffective in inhibiting glutathione peroxidase and glutathione reductase, while gold(III) compounds show some effect on glutathione peroxidase. The mitochondrial respiratory chain is scarcely affected by gold compounds while the other metal complexes and metal ions, in particular zinc ion and zinc pyrithione, show a more marked inhibitory effect that is reflected on a rapid induction of membrane potential decrease that precedes swelling. Therefore, differently from gold compounds, the various metal ions and metal complexes exert their effect on different targets indicating a lower specificity. It is concluded that gold compounds are highly specific inhibitors of mitochondrial thioredoxin reductase and this action influences other functions such as membrane permeability properties. Metal ions and metal complexes markedly inhibit the activity of thioredoxin reductase although to an extent lower than that of gold compounds. They also inhibit mitochondrial respiration, decrease membrane potential and, finally, induce swelling.

Animals↗

PubMedDate not supplied

Cellular neuroprotective mechanisms in cerebral ischemia: Bcl-2 family proteins and protection of mitochondrial function.

Mitochondria are central to brain cell response to ischemia, with critical roles in generation of ATP, production of free radicals, and regulation of apoptotic cell death. Changes in the permeability of the outer mitochondrial membrane to regulators of apoptosis can control ischemic cell death and this permeability is directly controlled by the Bcl-2 family of proteins. The Bcl-2 family regulate apoptosis by several mechanisms including affecting the formation of apoptotic protein-conducting pores in the outer mitochondrial membrane. The anti-apoptotic protein Bcl-2 improves neuron survival following various insults, and is protective even when administered after stroke onset in a rat model of focal ischemia. Despite intense study, the precise molecular mechanisms underlying protection by the anti-apoptotic members of the Bcl-2 family are not completely understood. This review focuses on the mechanisms by which Bcl-2 family members control the permeability of the mitochondrial membrane and influence other aspects of mitochondrial function after brain ischemia, concluding with discussion of the potential use of Bcl-2 for the treatment of cerebral ischemia.

Animals↗

PubMed2003

Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients.

BACKGROUND: Increased occurrence of several physical conditions has been reported in patients with depressive disorders. Various physical conditions and depressive disorder have been reported in patients with mitochondrial disorders. The aim of this study was to investigate mitochondrial function in selected depressed patients in search of an aetiological or pathophysiological factor common to both depression and physical symptoms. METHODS: Muscle biopsy was performed in 28 patients with a lifetime prevalence of major depressive disorder (MDD), and at least three chronic physical conditions that have been reported to be common in depressive as well as in mitochondrial disorders. Morphologic and biochemical investigations including mitochondrial ATP production rate (MAPR) by the bioluminometric method, spectrophotometric analyses of mitochondrial enzymes, and long-PCR and Southern blot techniques to detect mitochondrial DNA (mtDNA) deletions were performed. The Karolinska Scales of Personality (KSP) with 15 scales assessing vulnerability to psychopathology was filled in by 21 patients. RESULTS: Decreases of MAPR and enzyme ratios were found in the patients in comparison with controls (P<0.01). Deletions of mtDNA assessed with long-PCR were more frequent in patients than in controls (chi-square test P<0.05). Correlations were found between MAPR and the KSP scales 'Somatic Anxiety', 'Psychasthenia', and 'Suspicion' (P<0.01). LIMITATIONS: Results cannot be compared with previous studies, and cannot be generalized to all MDD patients. Individually matched controls were not available. CONCLUSIONS: The results suggest that mitochondrial dysfunction is associated with vulnerability to psychopathology in this selected patient group.

Adult↗

PubMed1999

An association between mitochondrial function and all-trans retinoic acid-induced apoptosis in acute myeloblastic leukaemia cells.

The present study investigated whether all-trans retinoic acid (ATRA)-induced apoptosis in acute myeloblastic leukaemia (AML) is related to changes in mitochondrial function. Two human AML cell lines, OU-AML-3 and OU-AML-7, known to be inducible to time-dependent apoptosis of varying degrees by ATRA, were used. Apoptosis induced by ATRA was shown to be a slow event. It was detected by the DNA electrophoretic method and cytofluorimetrical annexin V assay after 48 h exposure, and by morphology and polyADPribose polymerase (PARP) cleavage after 72 h exposure of AML cells to ATRA. The efflux of mitochondrial cytochrome c to cytosol was notable in Western blotting after 48 h exposure of the cells to ATRA and was observed before the drop in the mitochondrial membrane potential, which only took place after 72 h exposure, when measured by flow cytometry and a JC-1 probe. The apoptotic events in mitochondria were more evident in the OU-AML-3 than the OU-AML-7 cell line. This might relate to the different bcl-2 contents of the cell lines: the basic bcl-2 levels of the OU-AML-7 cell line were almost twofold compared to that of the OU-AML-3 cell line, as analysed by the ELISA method. However, both of the cell lines showed progressive down-regulation of bcl-2, which began after 12-24 h exposure of the cells to ATRA as determined by ELISA, Western blotting and flow cytometry. The present results show that mitochondria have a role in ATRA-induced apoptosis in AML cells and down-regulation of bcl-2 is related to it. In view of the previously published studies, the present results underline the fact that the timing of apoptotic events, such as fragmentation of DNA, externalization of phosphatidylserine, cytochrome c efflux, change in mitochondrial membrane potential and cleavage of PARP, are, to a notable extent, cell type and inducer-dependent.

Apoptosis↗

PubMed2004

Glucosamine-induced alterations of mitochondrial function in pancreatic beta-cells: possible role of protein glycosylation.

Chronic exposure of rat pancreatic islets and INS-1 insulinoma cells to glucosamine (GlcN) produced a reduction of glucose-induced (22.2 mM) insulin release that was associated with a reduction of ATP levels and ATP/ADP ratio compared with control groups. To further evaluate mitochondrial function and ATP metabolism, we then studied uncoupling protein-2 (UCP2), F1-F0-ATP-synthase, and mitochondrial membrane potential, a marker of F1-F0-ATP-synthase activity. UCP2 protein levels were unchanged after chronic exposure to GlcN on both pancreatic islets and INS-1 beta-cells. Due to the high number of cells required to measure mitochondrial F1-F0-ATP-synthase protein levels and mitochondrial membrane potential, we used INS-1 cells, and we found that chronic culture with GlcN increased F1-F0-ATP-synthase protein levels but decreased glucose-stimulated changes of mitochondrial membrane potential. Moreover, F1-F0-ATP-synthase was highly glycosylated, as demonstrated by experiments with N-glycosidase F and glycoprotein staining. Tunicamycin (an inhibitor of protein N-glycosylation), when added with GlcN in the culture medium, was able to partially prevent all these negative effects on insulin secretion, adenine nucleotide content, mitochondrial membrane potential, and protein glycosylation. Thus we suggest that GlcN-induced pancreatic beta-cell toxicity might be mediated by reduced cell energy production. An excessive protein N-glycosylation of mitochondrial F1-F0-ATP-synthase might lead to cell damage and secretory alterations in pancreatic beta-cells.

Adenine Nucleotides↗

PubMed2000

Changes in local cerebral blood flow, glucose utilization, and mitochondrial function following traumatic brain injury in rats.

The pathophysiology of secondary brain damage following experimental traumatic brain injury was investigated by measuring local cerebral blood flow (lCBF), local cerebral glucose utilization (lCGU), and activity of succinate dehydrogenase (SDH), which is a mitochondrial enzyme of the tricarboxylic acid cycle, in the rat brain after moderate lateral fluid percussion injury. Measurements used autoradiography for lCBF and lCGU with [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. Regional SDH activity was determined using quantitative imaging of formazan produced from 2,3,5-triphenyl tetrazolium chloride by SDH. lCBF decreased at 1 hour after injury and was significantly lower than the preinjury level in almost all regions of both hemispheres at 6 and 24 hours, and remained low at 2 weeks. lCGU increased 1 hour after injury but was significantly decreased at 6 and 24 hours, and at 2 weeks in most regions of both hemispheres. The ipsilateral hemisphere showed a significant decrease in the activity of SDH in the cortices, hippocampus, thalamus, and caudate/putamen, most conspicuously 72 hours after injury, whereas no significant decrease was observed in the contralateral hemisphere at any time. Necrosis in the injured cortex and reduction of the number of neurons in the ipsilateral hippocampus were observed 2 weeks after injury. The present study showed that a decrease in lCBF and mitochondrial dysfunction occur with glucose hypermetabolism around 1 hour after lateral fluid percussion injury, and that lCBF, lCGU, and mitochondrial function all deteriorate after 6 hours. This suggests that lCBF and cellular metabolism may change dynamically during the several hours following traumatic brain injury, and afterwards neuronal damage may result in an irreversible change in the areas with depressed glucose hypermetabolism in the early period after injury in combination with mitochondrial dysfunction.

Animals↗

PubMed1999

Glutathione depletion and neuronal cell death: the role of reactive oxygen intermediates and mitochondrial function.

Glutathione (GSH) levels are supposed to determine the vulnerability of many cells towards a wide array of insults. We investigated the effects of chronic inhibition of GSH synthesis and acute depletion of GSH on cerebellar granule neurons in vitro and determined cytoplasmic and mitochondrial GSH with relation to mitochondrial function and generation of reactive oxygen intermediates (ROI). l-buthionine sulfoximine (BSO), which irreversibly blocks gamma-glutamyl-cysteine synthase, led to a time- and concentration-dependent loss of cytoplasmic GSH, while mitochondrial GSH was relatively preserved. No increased generation of ROI was detected over 48 h and the mitochondrial membrane potential was largely maintained. Neuronal degeneration occurred when mitochondrial GSH levels had fallen below 50% of control after 24-36 h. In contrast, direct conjugation of mitochondrial and cytoplasmic GSH with etacrynic acid (EA), resulted in immediate loss of mitochondrial GSH, a large increase of ROI within 2 h, subsequent collapse of the mitochondrial membrane potential and complete cell death within 4-8 h. Electron microscopy studies revealed an as yet unknown change of the chromatin structure to a homogeneous granular pattern after BSO, while EA resulted in typical necrotic changes. No typical features of apoptosis, i.e., no chromatin condensation or DNA fragmentation were detected after GSH depletion after BSO or EA treatment.

Animals↗

PubMed2005

Effects of dietary coenzyme Q10 supplementation on hepatic mitochondrial function and the activities of respiratory chain-related enzymes in ascitic broiler chickens.

1. One hundred and sixty 1-d-old Arbor Acre male broiler chicks were fed with maize-soybean based diets for 6 weeks in a 2 x 2 factorial experiment. The factors were CoQ10 supplementation (0 or 40 mg/kg) and Escherichia coli lipopolysaccharide (LPS) challenge (LPS or saline). 2. CoQ10 was supplemented from d 1. From d 18, the chickens received three weekly i.p. injections of LPS (1.0 mg/kg BW) or an equivalent amount of sterile saline as control. From d 10 on, all chickens were exposed to low ambient temperature (12 to 15 degrees C) to induce ascites. 3. The blood packed cell volume and ascites heart index of broiler chickens were reduced by dietary CoQ10 supplementation. Mitochondrial State 3 and State 4 respiration, respiratory control ratio and phosphate oxygen ratio were not changed, but H+/site stoichiometry of complex II + III was elevated by dietary CoQ10 supplementation. 4. Cytochrome c oxidase and H+-ATPase activity were increased by CoQ10 supplementation, whereas NADH cytochrome c reductase and succinate cytochrome c reductase were not influenced. Mitochondrial anti-ROS capability was increased and malondialdehyde content was decreased by CoQ10 supplementation. 5. The work suggested that dietary CoQ10 supplementation could reduce broiler chickens' susceptibility to ascites, which might be the result of improving hepatic mitochondrial function, some respiratory chain-related enzymes activities and mitochondrial antioxidative capability.

Animal Feed↗

PubMed1997

Rigorous swim training impairs mitochondrial function in post-ischaemic rat heart.

The effect of rigorous swim training (6 h day-1, 5 days week-1 for an average of 191 h) on mitochondrial respiratory function was investigated in rat heart subjected to in vivo ischaemia reperfusion (I-R). Mitochondria was isolated from the risk region of the left ventricle subjected to 60 min occlusion of the main left coronary artery followed by 30 min reperfusion. Heart weight and heart-to-body weight ratio was increased by 21 and 28% (P < 0.01), respectively, in the trained (T, n = 15) vs. control rats (C, n = 20). I-R per se showed minimal effect on heart mitochondria regardless of training status. In sham, state 4 respiration rate was 26 and 32% (P < 0.05) lower in T vs. C rats, using malate-pyruvate (M-P) and 2-oxoglutarate (OG) as substrates, respectively. Training also reduced state 3 respiration by 28% (M-P) and 50% (OG) (P < 0.01). The respiratory control index (RCI) was unaltered in T with M-P, but decreased with OG (P < 0.01). In vitro exposure to superoxide radicals severely reduced state 4 and 3 respiration and RCI, but T hearts showed greater reductions of state 4 and 3 rates than C. Mitochondria from T hearts also revealed a greater state 4 inhibition by H2O2 and HO. compared with C. A lower glutathione content and a higher gamma-glutamyl transpeptidase activity (P < 0.05) was observed in T vs. C. It is concluded that rigorous swim training impairs heart mitochondrial function, making them more susceptible to in vivo and in vitro oxidative stress, and that this damaging effect may be related to a diminished glutathione reserve.

Animals↗

PubMed1977

On the formation of rho- petites in yeast. II. Effects of mutation tsm-8 on mitochondrial functions and rho-factor stability in Saccharomyces cerevisiae.

1. In non-fermentable substrates growth of mutant tsm-8 cells of Saccharomyces cerevisiae is restricted to about one generation after shift from 23 to 35 degrees C. Non-permissive conditions (35 degrees C, glycerol) cause a gradual decrease in respiration to about 20% of the activity at permissive temperature 23 degrees C). 2. Anaerobically grown and glucose-repressed mutant cells exhibit a decreased adaptation rate of mitochondrial functions to aerobic growth and non-fermentative growth, even at 23 degrees C, as revealed by determination of respiratory rates and mitochondrial protein synthesis. 3. At 35 degrees C, rho+ cells of mutant tsm-8 are converted to p- cells within 6-8 generations of growth, in all fermentable substrates tested. Drugs or antibiotics as nalidixic acid, acriflavin, chloramphenicol and erythromycin, bongkrecic acid, antimycin and FCCP, as well as anaerobiosis, have little or no influence on this kinetics. A heat shock does not yield rho- petites to a significant extent. 4. Reversion of tsm-8 cells to wild type function, which occurs spontaneously with a frequency of 10(-8), is found to be due to a mitochondrial mutational event.

Acriflavine↗

PubMed2005

Mitochondrial function and carotid body transduction.

Carotid body chemoreceptors respond to a decrease in arterial oxygen tension by increasing spiking activity on the sinus nerve. Our understanding of the oxygen-transducing ability of the organ arose from studies in the 1930s intended to understand how metabolic poisons stimulated breathing. Since that time, an intimate link between energy state and hypoxia sensing has been assumed and forms the basis of the metabolic hypothesis of oxygen sensing. This hypothesis is supported by studies demonstrating a loss of mitochondrial potential in carotid body cells at oxygen tensions that cause no change in cells from other tissues. Although the nature of the coupling between mitochondrial function and nerve excitation remains unresolved, experimental evidence supports roles for (1) release of mitochondrial calcium stores, (2) modulation of membrane channels that are linked to mitochondrial complexes I and IV, and (3) generation of signaling intermediates, such as reactive oxygen species (ROS) from complex I and III of the electron transport chain. If the mitochondrion is the oxygen-sensing site for peripheral chemoreceptors, then there exists the potential ability to manipulate, perhaps pharmacologically, the sensing function by alterations in expression of uncoupler proteins or chemicals that can alter the affinity of cytochrome oxidase for oxygen. Such manipulation may be useful for the treatment of hypoventilation syndromes or high altitude accommodation.

Acclimatization↗

PubMedDate not supplied

[Role of ATP-sensitive potassium channel activators in liver mitochondrial function in rats with different resistance to hypoxia].

Effects of ATP-sensitive potassium (KATP) channels opener pinacidil (0.06 mg/kg) and inhibitor glibenclamide (1 mg/kg) in rats with different resistance to hypoxia on indices of ADP-stimulation of mitochondrial respiration by Chance, calcium capacity and processes of lipid peroxidation in liver has been investigated. We used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate. Additional analyses contain the next inhibitors: mitochondrial fermentative complex I-10 mkM rotenone, succinate dehydrogenase 2 mM malonic acid. It was shown that effects of pinacidil induced the increasing of oxidative phosporylation efficacy and ATP synthesis together with lowering of calcium capacity in rats with low resistance to hypoxia. Effects of pinacidil were leveled by glibenclamide. These changes are connected with the increasing of respiratory rate, calcium overload and intensification of lipid peroxidation processes. A conclusion was made about protective effect of pinacidil on mitochondrial functioning by economization of oxygen-dependent processes, adaptive potentialities of organisms with low resistance to hypoxia being increased.

Adenosine Triphosphate↗