Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “OXIDATIVE PHOSPHORYLATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed1977

The effects of altered membrane sterol composition on oxidative phosphorylation in a haem mutant of Saccharomyces cerevisiae.

1. The sterol, unsaturated fatty acid and cytochrome contents of cells of a delta-aminolaevulinate synthase mutant of Saccharomyces cerevisiae are manipulated by growing the organism in media containing defined supplements of delta-aminolaevulinate and other porphyrin intermediates. 2. If unsaturated fatty acids are added to the growth medium as Tween 80, sterol content and respiratory cytochromes alone are manipulated. 3. In the presence of delta-aminolaevulinate (10-50mg/1) cells exhibit moderate to high respiratory activity, but growth yields are low, indicating a loss of oxidative phosphorylation. This is associated with the depletion of membrane lipids, either unsaturated fatty acids and sterols together or sterols alone. 4. Sterol depletion leads to the loss of coupled mitochondrial oxidative phosphorylation in vitro. 5. The lesion in oxidative phosphorylation is associated with an increase in the passive permeability of sterol-depleted mitochondria to protons. 6. Arrhenius plots of mitochondrial permeability to protons indicate that the activation energy for proton entry increases as the sterol content of the membranes decreases. 7. Studies on a cytoplasmic petite mutant isolated from strain ole-3, which lacks a functional membrane-bound protein-translocating adenosine triphosphatase, indicate that proton permeability of the petite mitochondria varies as a function of sterol composition in the same way as that of ole-3 grande mitochondria. This indicates that sterols alone are probably directly responsible for the increased proton entry, owing to a reorganization of the lipid in the membrane. 8. Supplemented ole-3 cells with a normal lipid composition and normal or higher than normal respiratory activities have a growth efficiency only 65% of that of the wild-type, indicating that a further lesion in energy metabolism may be present.

Aminolevulinic Acid↗
PubMed1996

In vitro interaction of nonsteroidal anti-inflammatory drugs on oxidative phosphorylation of rat kidney mitochondria: respiration and ATP synthesis.

The in vitro interference of some of most important nonsteroidal anti-inflammatory drugs (NSAIDs) with the respiration of rat kidney (renal cortex) mitochondria and ATP synthesis was evaluated. Acetylsalicylic acid, diclofenac sodium, mefenamic acid, and piroxicam both uncoupled and inhibited oxidative phosphorylation in mitochondria energized with glutamate plus malate or with succinate, while dipyrone only uncoupled and paracetamol only inhibited it. The drug concentrations affecting mitochondrial respiration were in the low to middle micromolar range for diclofenac, mefenamic acid, and piroxicam, and in the low millimolar range for acetylsalicylic acid, dipyrone, and paracetamol. The pattern of inhibition, except for the paracetamol, was similar to that expressed by the respiratory chain inhibitors. NSAIDs also inhibited the rate of ATP synthesis in mitochondria energized with glutamate plus malate, as well as the phosphorylation potential of mitochondria. The IC50 values for rate of ATP synthesis, using 2 mM ADP, were about 0.1 mM for diclofenac sodium and mefenamic acid, 0.7 mM for piroxicam, and in the range of 5-8 mM for acetylsalicylic acid, dipyrone, and paracetamol. The potential for renal energetic cytotoxicity of NSAIDs is discussed considering their ability to interact with the oxidative phosphorylation in rat renal cortex mitochondria. A comparison is made with the interference of salicylate, the main metabolite of acetylsalicylic acid, and a classical uncoupler of oxidative phosphorylation.

Acetaminophen↗
PubMed1984

Contributions of glycolysis and oxidative phosphorylation to adenosine 5'-triphosphate production in AS-30D hepatoma cells.

The AS-30D rat hepatoma cell line is characteristic of that class of rapidly growing tumors which exhibit high rates of aerobic glucose utilization and lactic acid production (Bustamante, E., Morris, H.P., and Pedersen, P.L., J. Biol. Chem., 256: 8699-8704, 1981). In this study, we have examined the coupling properties of the mitochondria in intact AS-30D hepatoma cells and the relative contributions of cytoplasmic (glycolytic) and mitochondrial compartments to total cellular ATP production in the presence of glucose and glutamine. All respiration in AS-30D cells was inhibited by inhibitors of mitochondrial electron transport, ruling out significant rates of respiration from other cellular components. Moreover, cellular respiration was found to be coupled to phosphorylation of ADP, as demonstrated by its inhibition by oligomycin and aurovertin, inhibitors of the mitochondrial ATP synthetase (F0F1-ATPase). When intact cells were supplied with glucose as the only added energy source, it was estimated that about 60% of the total cell ATP was derived from glycolysis and 40% from oxidative phosphorylation. Addition of physiological concentrations of glutamine in the presence of glucose had little effect on the relative contributions of glycolysis and oxidative phosphorylation to total cellular ATP production. In the absence of added glucose, glutamine alone could maintain the same ATP production rates by supporting mitochondrial oxidative phosphorylation. It is concluded that, in the AS-30D hepatoma cell line, glucose is the preferred energy source, with the larger portion of ATP production being supplied by glycolytic reactions. Although oxidative substrates such as glutamine can replace glucose in maintaining total cell ATP production, they do not appear to be the major fuel sources when hepatoma AS-30D cells are exposed to concentrations of substrates which occur in vivo.

Adenosine Triphosphate↗
PubMed1993

The nongenotoxic hepatocarcinogen Wy-14,643 is an uncoupler of oxidative phosphorylation in vivo.

Wy-14,643 is a potent nongenotoxic hepatic carcinogen and peroxisome proliferator in rodents; however, the mechanism by which it causes tumors remains unknown. In previous work it was demonstrated that Wy-14,643 caused a dose-dependent uncoupling of oxidative phosphorylation (half-maximal effect = 100 microM) in isolated mitochondria (Keller et al., 1992, Biochim. Biophys. Acta, 1162, 237-244); therefore, the purpose of this study was to determine if uncoupling occurred in vivo under conditions which lead ultimately to tumors. Rats were fed Wy-14,643 (0.1%) in ground laboratory chow for 1, 21, 75, and 105 days. As expected, activity of the peroxisomal marker enzyme, acyl-CoA oxidase, was increased about eightfold in liver homogenates during the first 3 weeks of treatment, confirming the induction of peroxisomes. Basal rates of oxygen uptake by the perfused liver were increased significantly by Wy-14,643 treatment at all time points studied, consistent with the hypothesis that oxidative phosphorylation was uncoupled. Basal rates of oxygen uptake of about 130 mumol/g/hr were increased by over 20 mumol/g/hr in rats fed Wy-14,643 in their diet for 10 weeks. Concomitantly, rates of urea synthesis from ammonia, a process highly dependent on ATP supply, were reduced significantly in the perfused liver from 104 mumol/g/hr in control livers to 13 mumol/g/hr in livers from rats treated with Wy-14,643 for 75 days. Taken together, these data indicate that energy supply is disrupted in vivo due to uncoupling of oxidative phosphorylation by Wy-14,643.

Acyl-CoA Oxidase↗
PubMed1988

Sigmoidal relation between mitochondrial respiration and log ([ATP]/[ADP])out under conditions of extramitochondrial ATP utilization. Implications for the control and thermodynamics of oxidative phosphorylation.

Except for close to state 3, mitochondrial respiration has been observed to vary almost linearly with the extramitochondrial phosphorylation potential. For the understanding of the control, thermodynamics, and stoichiometries of oxidative phosphorylation, it is important if this linearity corresponds to an extension of a near-equilibrium flow-force relationship. Using three methods to determine the extramitochondrial ATP/ADP ratio, we observed that at high ATP/ADP ratios the relationship between respiratory rate and log (ATP/ADP) deviated in a sigmoidal fashion from linearity, if the amount of hexokinase present was modulated. In a titration with uncoupler, the sigmoidicity at high ATP/ADP ratios was absent. This difference between the flow-force relationships of these two experiments suggests that the sigmoidicity in the former case reflects a nonproportional flow-force relationship of the adenine nucleotide translocator. In the latter case, one measures the flow-force relationship of the redox-driven proton pumps alone, which turns out to be virtually linear. We determined the flow-force relation of the adenine nucleotide translocator for two ways of varying the force and confirmed the sigmoidicity in both cases. The implication is that the near-linearity of the flow-force relationships at intermediary respiratory rates does not correspond to an Onsager-type (near equilibrium) linearity. We discuss that this phenomenon requires the application of nonclassical forms of nonequilibrium thermodynamics and may be responsible for some of the control over oxidative phosphorylation that is exerted by the cytosolic ATP consuming processes.

Adenosine Diphosphate↗
PubMed1981

Oxidative phosphorylation, enzyme induction and rat liver regeneration: effect of phenobarbital.

In order to outline the relationship between oxidative phosphorylation, enzyme induction and rat liver regeneration, the effect of one single dose of phenobarbital (PB) on hepatic mitochondria, microsomes and DNA synthesis was investigated. Experiments were performed on intact and partially hepatectomized rats. Results and conclusions can be summarized as follows: (1) While PB has no consistent effect on mitochondrial respiration either in normal or in partially hepatectomized rats, it clearly enhances at the rate of DNA synthesis in hepatectomized rats at 24 h. This suggests that the effect of PB on DNA synthesis is independent from the mitochondrial ATP generating activity. (2) PB causes the accumulation of cytochrome P-450 in intact rat hepatocytes, but this effect is suppressed by partial hepatectomy during the first 24 h. This and the above observation on mitochondria suggest that enzyme induction in these experimental conditions is not associated with an increase in mitochondrial oxidative phosphorylation. (3) The mechanism of the influence of PB on DNA synthesis is unclear, but present data suggest that in one single dose PB may behave in two different ways: in intact liver it causes the accumulation of cytochrome P-450 and in partially resected liver it enhances the rate of DNA synthesis; mitochondria playing apparently no important role in this interaction.

Animals↗
PubMed1984

Effects of ATP on various steps controlling the rate of oxidative phosphorylation in newborn rat liver mitochondria.

Preincubation of newborn rat liver mitochondria with ATP increases their state 3 respiration rate [J. K. Pollak (1975) Biochem. J. 150, 477-488; J. R. Aprille, and G. K. Asimakis (1980) Arch. Biochem. Biophys. 201, 564-575]. To determine which reactions contribute to control the rate of succinate oxidation with and without prior exposure to ATP, the effects of inhibitors specific for various reactions were studied. The adenine nucleotide translocator does not control the respiration in newborn more than in the adult mitochondria. The supply of reducing equivalents to the respiratory chain is an important step controlling the rate of oxidative phosphorylation by mitochondria from newborn rat liver, especially after preincubation with ATP. On the contrary, titrations with oligomycin show that the preincubation with ATP markedly decreases the control exerted by the ATPase-ATP synthase complex. That the rate of ATP synthesis is one of the steps controlling the rate of oxidative phosphorylation in newborn rat liver mitochondria is in striking contrast to the behavior of adult rat liver mitochondria. Other differences include a greater permeability to protons and a marked increase in sensitivity to mersalyl, indicating an easier accessibility of the proteins involved in oxidative phosphorylation to the thiol reagent.

Adenosine Triphosphate↗
PubMed1996

Stimulation of GLUT1 glucose transporter expression in response to inhibition of oxidative phosphorylation: role of reduced sulfhydryl groups.

Treatment of Clone 9 cells incubated in the absence of serum with 5 mM azide for 24 h results in an 8- and 3-fold induction in GLUT1 mRNA and GLUT1 protein, respectively. To explore the pathways mediating the induction of GLUT1 mRNA, we first examined whether inhibition of oxidative phosphorylation by other agents results to a similar response. Exposure of cells to 5 microM carbonyl cyanide m-chlorophenylhydrazone (CCCP), 0.15 microM oligomycin B, or 5 mM azide resulted in near-equivalent increases in GLUT1 mRNA content. The inhibition of oxidative phosphorylation is associated with increased cell lactate content and in extracellular lactate to pyruvate ratio, reflecting a rise in cytosolic NADH/NAD+ ratio. We next tested the possibility that an increase in cell SH/SS ratio mediates the enhancement of GLUT1 mRNA in response to azide. We show that treatment of cells with 10 mM mercaptoethanol, an agent that increases cell SH/SS ratio, results in a approximately 6-fold increase in GLUT1 mRNA content. Moreover, incubation of cells in the presence of 0.3 mM diamide, a known intracellular sulfhydryl oxidizing agent, completely abolishes the induction of GLUT1 mRNA by azide. The results suggest that an increase in cell SH/SS ratio plays a critical role in the induction of GLUT1 mRNA in response to inhibition of oxidative phosphorylation.

Animals↗
PubMed1993

Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 2. Uncoupling effect on oxidative phosphorylation of liver mitochondria.

Effects of 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) on hepatic mitochondrial oxidative phosphorylation in vitro, and on hepatic peroxisomal enzymes activities and microsomal mixed-function oxidase activities were studied. 1. A low concentration of MBEBP, less than 50 microM, increased state 4 respiration and decreased state 3 respiration. However, a higher concentration of MBEBP, greater than 100 microM, acted as a respiratory inhibitor. Therefore, MBEBP was found to act as an uncoupler of oxidative phosphorylation in rat liver mitochondria. 2. MBEBP significantly decreased peroxisomal enzymes, cyanide-insensitive palmitoyl-CoA oxidizing activity and catalase activity in the livers of rats fed 0.2, 1.0 or 5.0% MBEBP for 4 weeks. 3. In microsomal enzyme assay, NADPH cytochrome c reductase activity was significantly increased, however, cytochrome P-450, cytochrome b5 levels, aminopyrine N-demethylase and benzo [a] pyrene hydroxylase activities were not significantly increased in the livers of rats fed 1.0 or 5.0% MBEBP for 4 weeks. The weight loss and the decrease of serum triglyceride level observed in the MBEBP-treated rats seemed to be caused by its uncoupling effects, which might also be the cause of the testicular damage induced by MBEBP.

Animals↗
PubMed1984

Control of mitochondrial oxidative phosphorylation.

The objective of this investigation is to analyze the two following problems of the regulation of mitochondrial oxidative phosphorylation: what is the extramitochondrial parameter that controls ATP production according to the cytoplasmic demands and how the control is distributed between various mitochondrial enzymes. On the basis of the data of Groen et al. (1982) it is shown that as the respiration rates ranged over 30-50% of the maximum (i.e. within the physiological region) the contribution of the adenine nucleotide translocator to the control of the ATP flux is no less than 90%, referring to the total contribution of all mitochondrial enzymes as 100%. Founding on the key role of the adenine nucleotide translocator it has been concluded that besides the extramitochondrial [ATP]/[ADP] ratio the absolute ADP concentration is another extramitochondrial signal controlling significantly the rate of oxidative phosphorylation.

Adenosine Diphosphate↗
PubMedDate not supplied

Abnormalities of oxidative phosphorylation due to excess of deficiency of thyroid hormones.

ATP synthesis requires the presence of thyroid hormones that activate oxidative phosphorylation. ATP supports the energy consuming reactions such as actin-myosin interaction, calcium and sodium pump, which are essential in a normal heart function. Thyroid insufficiency depresses mitochondrial oxidation, leading to ATP depletion which can not be compensated by activated glycolysis. Glycolysis under conditions of hypoxia due to accumulation of lactate or NADPH, impairs membrane permeability and mitochondrial function, causing enzyme release and pump failure. In severe hyperthyroidism an ATP deficiency occurs by uncoupling of oxidative phosphorylation, T4 stimulating the extra-mitochondrial metabolic pathways. There is a disproportion between consumption of O2 and nutrients and ATP production. The T4--T3 excess via trace metal (magnesium, copper, zinc, iron, etc.) chelation inhibits enzyme activity which had impaired ATP synthesis. At the same time the excess of T4 by stimulating ATP-ase causes heat release and dissipation of ATP, favouring cardiothyreosis.

Adenosine Triphosphate↗
PubMed1985

Energy-independent protection of the oxidative phosphorylation capacity of mitochondria against anoxic damage by ATP and its non-metabolizable analogs.

Preservation of the oxidative phosphorylation capacity of mitochondria by addition of ATP under anaerobic conditions was analyzed by use of non-metabolizable adenine nucleotide analogs. The capacity was well preserved in the presence of ATP and did not require the hydrolysis of ATP, since ATP analogs, such as beta, gamma-methylene adenosine triphosphate (AMPPCP), alpha, beta-methylene adenosine triphosphate (AMPCPP), and adenylyl imidodiphosphate (AMPPNP), were as effective as ATP. These analogs were incorporated into mitochondria through ATP/ADP translocase to maintain the original level of total adenine nucleotides in the mitochondria. ADP apparently had the same effect as ATP, but its effect was shown to be due to ATP generated from it by adenylate kinase in mitochondria. An analog of ADP, alpha, beta-methylene adenosine diphosphate (AMPCP), which was found to be a substrate of the translocase but not of adenylate kinase, could not replace ADP or ATP. From these results, it was concluded that the oxidative phosphorylation capacity of mitochondria was maintained by ATP, but not ADP, through a process not requiring energy.

Adenosine Diphosphate↗
PubMed1983

Inhibition of oxidative phosphorylation by a Ca2+-induced diminution of the adenine nucleotide translocator.

The mechanism through which internal Ca2+ inhibits oxidative phosphorylation of rat heart mitochondria has been explored. In parallel to a Ca2+-induced diminution of the activity of the adenine nucleotide translocator, an efflux of internal adenine nucleotides is observed. The efflux of adenine nucleotides depends on the amount of Ca2+ accumulated by the mitochondria and on the time that Ca2+ remains in the mitochondria; this efflux is atractyloside insensitive. These results suggest that internal Ca2+, by inducing a lowering of the internal concentration of adenine nucleotides, diminishes the rate of exchange of adenine nucleotides via the translocase, and in consequence of oxidative phosphorylation. Under conditions in which the Ca2+-induced release of adenine nucleotides takes place, no gross changes of the permeability properties of the membrane are observed. As revealed by studies with arsenate, respiratory activity and the function of the ATPase in the direction of ATP synthesis are not affected by internal Ca2+.

Adenine Nucleotides↗
PubMedDate not supplied

[Oxidative phosphorylation capacity of Rhodopseudomonas palustris during growth in light and darkness].

Assimilation of oxygen by the cells of Rhodopseudomonas palustris grown in the light and in the darkness is stimulated by p-chlorocarbonylcyanidephanylhydrazone, suggesting respiration coupled to phosphorylatin. Membranes of the cells grown in the light are capable of oxidative phosphorylation in the course of electron transport from NADH and succinate to O2 with P/O being 0.03 and 0.20, respectively. Membranes of the cells grown in the darkness in aerobic conditions are capable of oxidative phosphorylation in the presence of NADH, succinate and ascorbate + phenazinemetasulphate with P/O being 0.25, 0.40 and 0.06, respectively. Phosphorylation during oxidation of ascorbate + phenazinemetasulphate in the cells grown in the darkness suggests that the third point of coupling has appeared as a result of synthesis of cytochrome a. There are only minor differences in phosphorylation in the membranes of the cells grown in the light and in the darkness, as was shown by its susceptibility to p-chlorocarbonylcyanidephenyl-hydrazone, oligomycin, antimycin A and cyanide.

Antimycin A↗
PubMed2000

Tissue variation in the control of oxidative phosphorylation: implication for mitochondrial diseases.

Metabolic control analysis has often been used for quantitative studies of the regulation of mitochondrial oxidative phosphorylations (OXPHOS). The main contribution of this work has been to show that the control of mitochondrial metabolic fluxes can be shared among several steps of the oxidative phosphorylation process, and that this distribution can vary according to the steady state and the tissue. However, these studies do not show whether this observed variation in the OXPHOS control is due to the experimental conditions or to the nature of the mitochondria. To find out if there actually exists a tissue variation in the distribution of OXPHOS control coefficients, we determined the control coefficients of seven OXPHOS complexes on the oxygen-consumption flux in rat mitochondria isolated from five different tissues under identical experimental conditions. Thus in this work, only the nature of the mitochondria can be responsible for any variation detected in the control coefficient values between different tissues. The analysis of control coefficient distribution shows two tissue groups: (i) the muscle and the heart, controlled essentially at the level of the respiratory chain; and (ii) the liver, the kidney and the brain, controlled mainly at the phosphorylation level by ATP synthase and the phosphate carrier. We propose that this variation in control coefficient according to the tissue origin of the mitochondria can explain part of the tissue specificity observed in mitochondrial cytopathies.

Animals↗
PubMed1978

Sidedness of inhibition of energy transduction in oxidative phosphorylation in rat liver mitochondria by ethidium bromide.

Ethidium bromide, a new type of inhibitor of energy transduction in oxidative phosphorylation, inhibited ATP synthesis in intact mitochondria but not in submitochondrial particles, the latter being inside-out relative to the membranes of intact mitochondria. Ethidium bromide incorporated inside the submitochondrial particles inhibited ATP synthesis in the particles. The decrease of the membrane potential by valinomycin (plus KCl) inhibited only slightly the energy-dependent binding of ethidium bromide to the mitochondria. The present results show clearly that ethidium bromide inhibited energy transduction in oxidative phosphorylation by acting on the outer side (C-side) of the inner mitochondrial membrane, perhaps by neutralizing negative charges created on the surface of the C-side, and that it had no inhibitory activity on the inner side (M-side) of the membrane. Th present results show also that the energy-dependent binding of ethidium is not due to electrophoretic transport down the membrane potential; ethidium may bind to negative charges on the surface of the C-side. The present study suggest that an anisotropic distribution of electric charge in the inner mitochondrial membrane is an intermediary high energy state of oxidatvie phosphorylation.

Adenosine Triphosphate↗
PubMed1991

Effects of N-tricyanovinylamines on oxidative phosphorylation and level of SH-groups in rat liver mitochondria.

The effects of N-substituted tricyanovinylamines on oxidative phosphorylation as well as on glutathione and total SH group concentrations in rat liver mitochondria was studied. The N-TCVA derivatives studied (N-cyclohexyl; N-isobutyl; N-benzyl; N-phenyl; N-4-Br-phenyl; N-3-nitrophenyl) had an uncoupling effection on the oxidative phosphorylation. They stimulated the respiration of mitochondria and influenced their membrane potential. In their property as SH agents, the N-TCVA derivatives reduced the level of TSH groups of the mitochondria present in concentrations of 2 mumol/mg protein. The activity of succinate dehydrogenase was decreased by N-TCVA by 13%. N-TCVA derivatives changed the redox state of glutathione in mitochondria. This effect was observed at the concentration 0.3 mumol/mg protein. The results obtained in the present study support the view that the glutathione status is more sensitive than the total level of SH groups to incubation of mitochondria with SH agents such as N-TCVA derivatives.

Amines↗