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At least 487 records · Page 27Linked to original sources
PubMed1983

Phloretin - an uncoupler and an inhibitor of mitochondrial oxidative phosphorylation.

The effect of phloretin on respiration by isolated mitochondria and submitochondrial particles was studied. In submitochondrial particles, both NADH- and succinate-dependent respiration was inhibited by phloretin. 50% maximum inhibition was reached at phloretin concentrations of 0.1 mM (NADH oxidation) and 0.7 mM (succinate oxidation). In isolated mitochondria, phloretin inhibited glutamate oxidation in both State 3 and State 4; 50% maximum inhibition occurred at about 30 microM. Succinate oxidation is inhibited in State 3 by phloretin, inhibition being half its maximum value at 0.5 mM, but in State 4 it is stimulated about 2-fold by phloretin at a concentration of 0.6 mM. Ascorbate oxidation is stimulated in both State 3 and State 4, maximum stimulation being equal to that obtained with an uncoupler of oxidative phosphorylation. Under all circumstances, phloretin lowered the transmembrane electrical potential difference in isolated mitochondria. These results are discussed in terms of mosaic non-equilibrium thermodynamics. We conclude that phloretin is both an uncoupler and an inhibitor of oxidative phosphorylation.

Animals↗
PubMed1965

EFFECTS OF TETRAZOLIUM SALTS ON OXIDATIVE PHOSPHORYLATION IN RAT-LIVER MITOCHONDRIA.

1. The effects of five different tetrazolium salts on oxidative phosphorylation in rat-liver mitochondria have been investigated. 2. In all cases the mitochondria were uncoupled by very low concentrations of the tetrazolium salts. Further, the transition from a system just exhibiting respiratory control to one in which the mitochondria were totally uncoupled has been shown to occur over very small concentration ranges of the tetrazolium salts. 3. The effectiveness of the five tetrazolium salts as uncoupling agents is discussed in the light of their standard electrode potentials and effectiveness as electron acceptors in dehydrogenase-linked reactions.

Hydroxybutyrates↗
PubMed2003

Mitochondrial oxidative phosphorylation: pitfalls and tips in measuring and interpreting enzyme activities.

Mitochondrial oxidative phosphorylation (OXPHOS) is fundamental in all aspects of cellular life in aerobic cells and organisms. It is therefore not surprising that a variety of diseases have been attributed to dysfunction of the OXPHOS enzymes. Assessment of OXPHOS in human samples has proved to be a difficult task over years, even when relying on well-established methods. The complexity and the flexibility of the mitochondrial organization in cells account for a large part in the difficulties encountered in assessing OXPHOS activity. Nevertheless, a careful and detailed analysis of OXPHOS enzyme activity in cells or biopsy samples from patients at risk provides diagnosis of potential OXPHOS deficiency. Problems inherent in the use of human material, mostly the small size of the samples to be analysed, are difficult to resolve. However, cautious handling of these samples permits reasonable confidence to be reached in the interpretation of the data.

Adenosine Triphosphate↗
PubMed1993

Functional characterization of mitochondrial oxidative phosphorylation in saponin-skinned human muscle fibers.

The conditions of treatment of human skeletal muscle fibers from M. vastus lateralis with saponin were optimized to achieve complete permeabilization of cell membrane at intact mitochondrial oxidative phosphorylation. After 30 min of incubation with saponin all lactate dehydrogenase, 50% of creatine kinase, 30% of adenylate kinase and less than 20% of citrate synthase was released into the permeabilization medium. These skinned fibers behave similar to isolated mitochondria from human skeletal muscle: (i) the respiration with mitochondrial substrates can be stimulated by ADP, (ii) inhibited by carboxyatractyloside and (iii) it is possible to detect fluorescence changes of mitochondrial NAD(P)H on additions of substrates, uncoupler and cyanide. From a comparison of rates of respiration per cytochrome aa3 content of isolated human skeletal muscle mitochondria and saponin-skinned muscle fibers it was possible to calculate that almost 85% of mitochondria in those fibers are accessible for the investigation of oxidative phosphorylation. As shown by the investigation of biopsy samples of two patients with undefined myopathies these fibers are a suitable object for the replacement of isolated mitochondria in the diagnosis of mitochondrial myopathies and encephalomyopathies.

Animals↗
PubMed1965

Uncouplers of rat-liver mitochondrial oxidative phosphorylation.

1. The ability of a series of compounds to uncouple oxidative phosphorylation of rat-liver mitochondria has been investigated. 2. The compounds were: 2-amino-1,1,3-tricyanopropene; carbonyl cyanide phenylhydrazone and its m-chloro and p-trifluoromethoxy derivatives; 4,5,6,7-tetrachloro-, 5-chloro-4-nitro-, 5-nitro-and 4,5,6,7-tetrachloro-1-methyl-benzotriazole; 4-hydroxy-3,5-di-iodo-, 3,5-di-bromo-4-hydroxy- and 3,5-dichloro-4-hydroxy-benzonitrile; and pentafluorophenol. 3. In a medium the components and physical condition of which were, as far as possible, kept constant, each compound was tested for ability to stimulate adenosine triphosphatase, to stimulate respiration in the presence of pyruvate as substrate, to inhibit phosphate uptake and to prevent swelling by trimethyltin. 4. Each compound was also examined with respect to its ability to produce rapid rigor mortis in mice. 5. The biological properties were compared with the dissociation constant and the hexane-water partition coefficient for each compound. 6. With the exception of 4,5,6,7-tetrachloro-1-methylbenzotriazole, all the compounds behaved qualitatively as 2,4-dinitrophenol. 7. Within each class of compound there is a relation between biological activity and the physical attributes measured. 8. The most efficient uncouplers were the most acidic and the most hydrophobic.

Animals↗
PubMedDate not supplied

[Effect of hydrocortisone and insulin on changes of oxidative phosphorylation after neutron irradiation].

Total double irradiation of rats with a fast neutron flow does not affect oxidative phosphorylation in the liver mitochondria but causes an essential decrease in the intensity of phosphorylation in mitochondria and chemoluminescence in blood serum of animals. Postradiation multiple administration of hydrocortisone intensifies the radiation inhibition of oxidation and phosphorylation of mitochondria and insulin administration stimulates phosphorylation in the liver mitochondria and the intensity of chemoluminescence in blood serum of rats. Hydrocortisone in combination with insulin has a less pronounced stimulating effect on phosphorylation than insulin, but the intensity of chemoluminescence in this case is higher than under the effect of each preparation separately.

Animals↗
PubMed1984

Conformational coupling in H+-pumps and ATP synthesis--its analysis with anisotropic inhibitors of energy transduction in oxidative phosphorylation.

The analysis of anisotropic inhibitor-induced phenomena in mitochondria revealed that two kinds of negative charges are generated near surface of the C-side of mitochondrial inner membranes in the energized state, on the redox complexes (I, III & IV) and F0, respectively, and that positively charged anisotropic inhibitors (AI+) inhibit energy transduction in oxidative phosphorylation by binding to these negative charges. Thus, AI+ have two different inhibition sites in oxidative phosphorylation, the redox complexes and F0. The membrane components generating the negative charges in energized mitochondria were examined by the technique of photoaffinity labeling with monoazide ethidium, which is an AI+. Results showed that monoazide ethidium specifically binds to two kinds of hydrophobic protein (of 8 K and 13 K daltons) of mitochondria energized with succinate, and these proteins were named chargerin I and II, respectively. Chargerin I and II, which may be components of the redox complexes and Fo, seem to generate the negative charges described above, and these may be essential for H+-pumps in the redox complexes and F1 X F0. AI+ seem to inhibit ATP synthesis by binding to negatively charged sites of chargerin I and II. Based on these findings and the salient results on energy-transducing membranes obtained recently in other laboratories, a conformational model of H+-pumps and ATP synthesis in mitochondria is proposed, which is also applicable to ATP synthesis in other energy-transducing membranes and ATP-linked active transport of ions.

Adenosine Triphosphate↗
PubMed1980

Ionophore A23187 induced reductions in toad urinary bladder epithelial cell oxidative phosphorylation and viability: implications for A23187 related declines in epithelial active transport.

The divalent cation ionophore A23187 increased oxygen consumption by isolated epithelial cells from toad urinary bladder, and increase similar to that seen with 2,4-dinitrophenol, a classic uncoupler of mitochondrial oxidative phosphorylation. This respiratory stimulation was not seen in calcium-free incubation media. That this A23187 induced rise in cell oxygen consumption was due to a primary uncoupling action on mitochondrial oxidative phosphorylation rather than secondary to stimulation of cellular transport processes and mediated via increased cellular ADP levels was suggested by the ability of A23187 to release the inhibition of cellular respiration by oligomycin, an inhibitor of the mitochondrial proton ATPase which blocks the stimulation of mitochondrial respiration by ADP. Since active transepithelial ion transport and cellular energy production are closely linked processes, the uncoupling action of A23187 in the presence of extracellular calcium is sufficient to account for an acute decline in active ion transport across epithelia without invoking other calcium-mediated processes. Furthermore, isolated epithelial cells exposed to A23187 for 90 min had greater than 50% loss of viability, as measured by failure of Trypan blue exclusion. The subacute A23187 induced declines in transepithelial transport, therefore, may be secondary to its non-specific effects on cell viability.

Animals↗
PubMed2002

Effect of hypoenergetic feeding on muscle oxidative phosphorylation and mitochondrial complex I-IV activities in rats.

BACKGROUND: Previous studies showed that malnutrition reduces the activity of complexes I, II, and III in the mitochondria of skeletal muscle. OBJECTIVE: We hypothesized that malnutrition would influence oxidative phosphorylation and mitochondrial complex activity in the skeletal muscle of rats. DESIGN: Thirty-two rats were assigned either to a control group with an ad libitum intake of 364 kJ/d or to a hypoenergetic group with an intake of 92 kJ/d. Eleven of these rats received the hypoenergetic diet for 10 d, 2 for 5 d, 2 for 6 d, 2 for 7 d, and 1 each for 8 and 11 d to achieve a distributed weight loss. Ten controls were fed for 10 d, 2 for 7 d, and 1 for 5 d, to match day 10, day 5, and the midpoint (day 7) of 6-8 d of hypoenergetic feeding. The 2 diets provided the same volume, electrolytes, vitamins, and trace elements but different amounts of energy. RESULTS: A significant relation was observed between weight loss and the state 4 and 3 oxidation rates with pyruvate + malate and for state 3 glutamate + malate and succinate + rotenone but not with tetramethyl-p-phenylenediamine + ascorbate + antimycin A (TMPD). Similarly, a significant relation was observed between the degree of weight loss and complex I and III activities but not with complex II and IV activities. CONCLUSIONS: The complex activities of the mitochondrial oxidative phosphorylation chain in muscle were depressed selectively with energy deprivation when compared with normally fed rats. These findings may partly explain the mechanism of reduced muscle energetics in energy malnutrition.

Animals↗
PubMed1993

[Oxidative phosphorylation uncoupling in hyperthyroidism as a result of activating cyclosporin-sensitive pores in the inner mitochondrial membrane by water soluble modulators from rat liver cytoplasm].

Small concentrations of low molecular weight modulators of the functional state of rat liver cytoplasm mitochondria, which uncouple oxidative phosphorylation, induce phosphate-dependent transport of potassium and hydrogen ions. In contrast, high concentrations of these compounds induce nonspecific transport of monovalent cations and sucrose (K+ > H+ > Na+ > or = Li+ > sucrose). The effect of cytoplasmic modulators on oxidative phosphorylation and permeability of the inner mitochondrial membrane in inhibited by cyclosporin A and controlled by physiological concentrations of Ca2+. It is assumed that ion transport across the inner mitochondrial membrane in the presence of cytoplasmic modulators is implemented by the same cyclosporin-sensitive transport system which in damaged mitochondria functions as a nonspecific pore.

Animals↗
PubMed2002

Mass spectrometric identification of mitochondrial oxidative phosphorylation subunits separated by two-dimensional blue-native polyacrylamide gel electrophoresis.

Blue-native polyacrylamide gel electrophoresis is a powerful tool for the separation of intact membrane protein complexes mainly applied to the analysis of the enzymes of the mitochondrial oxidative phosphorylation system (OXPHOS). Combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), it reveals a two-dimensional pattern showing the individual subunits of the five OXPHOS multi-enzyme complexes. This pattern is useful in the diagnostic analysis of several diseases related to disorders in the oxidative phosphorylation system. However, in order to use this method for systematic diagnostic purposes and to be able to link disease with absence or reduced expression of specific subunits, an unambiguous identification of the individual subunits is necessary. In this study, we completed this task, implementing peptide mass fingerprinting and mass spectrometric sequence analysis. In the course of these analyses, we discovered a novel variant of a cytochrome c oxidase subunit VIc.

Electron Transport Complex IV↗
PubMed1978

Energy coupling in liver mitochondria from dystrophic mice: differential sensitivity of oxidative phosphorylation and Ca2+ uptake to K+.

Studies were carried out to examine oxidative phosphorylation, cation uptake, and electrokinetic properties of liver mitochondria from genetically dystrophic mice in comparison with those from livers of littermate controls. While no differences were seen with respect to the rates of substrate oxidation, ADP/oxygen ratio, and RCl and cytochrome content, the mitochondria from the dystropic group were characterized by an elevated basal ATPase activity in the presence of NaCl. Additionally, these mitochondria were highly sensitive to high concentrations of exogenously added K+ that, besides stimulating state 4 respiration, caused uncoupling in the mitochondria. These mitochondria accumulated Ca2+ at a higher rate, and unlike the controls, Ca2+ uptake was not sensitive to exogenously added K+. It was also observed that the net negative charge on mitochondria decreased significantly in the dystrophic state. It is thus apparent that muscular dystrophy manifests itself also in terms of alteration in the membrane properties of liver mitochondria.

Adenosine Diphosphate↗
PubMed1984

Biochemical effects of PR toxin on rat liver mitochondrial respiration and oxidative phosphorylation.

The in vitro effects of PR toxin, a toxic secondary metabolite produced by certain strains of Penicillium roqueforti, on the membrane structure and function of rat liver mitochondria were investigated. It was found that the respiratory control and oxidative phosphorylation of the isolated mitochondria decreased concomitantly when the toxin was added to the assay system. The respiratory control ratio decreased about 60% and the ADP/O ratio decreased about 40% upon addition of 3.1 X 10(-5) M PR toxin to the highly coupled mitochondria. These findings suggest that PR toxin impairs the structural integrity of mitochondrial membranes. On the other hand, the toxin inhibited mitochondrial respiratory functions. It exhibited noncompetitive inhibitions to succinate oxidase, succinate-cytochrome c reductase, and succinate dehydrogenase activities of the mitochondrial respiratory chain. The inhibitory constants of PR toxin to these three enzyme systems were estimated to be 5.1 X 10(-6), 2.4 X 10(-5), and 5.2 X 10(-5) M, respectively. Moreover, PR toxin was found to change the spectral features of succinate-reduced cytochrome b and cytochrome c1 in succinate-cytochrome c reductase and inhibited the electron transfer between the two cytochromes. These observations indicate that the electron transfer function of succinate-cytochrome c reductase was perturbed by the toxin. However, PR toxin did not show significant inhibition of either cytochrome oxidase or NADH dehydrogenase activity of the mitochondria. It is thus concluded that PR toxin exerts its effect on the mitochondrial respiration and oxidative phosphorylation through action on the membrane and the succinate-cytochrome c reductase complex of the mitochondria.

Animals↗
PubMed1991

[Features of oxidative phosphorylation in brain mitochondria of rats with different sensitivity to oxygen insufficiency].

Oxidative phosphorylation parameters have been investigated in the isolated brain mitochondria of rats preliminary divided into non-resistant (NR) and high-resistant (HR) animals by their sensitivity to hypobaric hypoxia. During the NAD-dependent substrates oxidation it was shown that the identical effectiveness of the respiratory chain function in both groups of animals was reached at more tension of the oxidative processes. It has been established that at the identical effectiveness of the succinate oxidation by the brain mitochondria in both groups of animals compensatory potentialities of the succinate-oxidase pathway of oxidation is higher in the brain of the NR to hypoxia animals. It has been shown the regulated influence of the NAD-dependent pathway of oxidation activity on the succinate-oxidase site of respiratory chain. This influence is more expressed in the brain mitochondria of the NR animals that in the HR animals.

Animals↗
PubMed1992

Dual function of a new nuclear gene for oxidative phosphorylation and vegetative growth in yeast.

A new gene essential for cell viability and indispensable for the biogenesis of a functional respiratory chain in Saccharomyces cerevisiae was isolated by complementing a temperature-sensitive mutant. This conditional nuclear mutation selectively affects oxidative phosphorylation at restrictive temperatures. At the molecular level a severe and complex defect inside mitochondria is observed, with drastically reduced levels of mitochondrial transcripts. Surprisingly a null mutation in this nuclear gene in a haploid yeast strain leads to cell death. Spores containing a disrupted copy of the gene exhibit a severe growth defect and cell division stops irreversibly after 3 to 4 days. It is shown that the null and conditional mutants are indeed allelic. This finding demonstrates a dual function of the gene product in oxidative phosphorylation and vegetative growth. The putative protein product, as deduced from the sequence of the relevant reading frame is characterized by a low molecular weight of approximately 14 kDa, a high content of charged amino acids and a very low codon bias index. A transcript of low abundance and with a length of about 600 nucleotides can be assigned to this gene.

Amino Acid Sequence↗
PubMed1975

The rapid labeling of adenosine triphosphate by 32P-labeled inorganic phosphate and the exchange of phosphate oxygens as related to conformational coupling in oxidative phosphorylation.

Evidence is presented that extends and amplifies the concept that in oxidative phosphorylation energy input serves to bring about release of ATP formed at a catalytic site by reversal of hydrolysis. The evidence with beef heart submitochondrial particles includes additional demonstration of uncoupler insensitive Pi leads to HOH exhchange, demonstration that this exchange is sensitive to the specific phosphorylation inhibitor, oligomycin, and demonstration that the small burst of uncoupler-insensitive ATP, rapidly labeled after addition of a tracer of 32Pi, behaves in a manner consistent with its participation as a membrane-bound intermediate in the Pi leads to HOH exchange. In addition, data are presented showing that addition of hexokinase plus glucose to submitochondrial particles in presence of ADP and Pi considerably lowers the Pi leads to HOH exchange but that further addition of cyanide or 2,4-dinitrophenol or both has little additional effect. Such data are compatible with no energy requirement for formation of bound ATP. However, with a large excess of hexokinase, the rate of the Pi leads to HOH exchange is further depressed. This could reflect some use of energy to promote formation of ATP at the catalytic site or to maintain the integrity of the phosphorylation system. Relationships of these findings to related information in the field are discussed.

Adenosine Triphosphate↗
PubMed1980

[Interactions between heart mitochondrial creatine kinase and oxidative phosphorylation].

The conditions for chromatographic separation in Silufol plates of adenine nucleotides, creatinine phosphate, glucose-6-phosphate and Pi have been found. Using this method, it was shown that in the presence of Pi and non-labelled ATP the specific radioactivity of creatine phosphate formed by mitochondrial creatinine kinase via oxidative phosphorylation increases at the same rate as does the specific radioactivity of the surrounding solution of ATP. It is concluded that under the given experimental conditions the ATP formed via oxidative phosphorylation enters the enzyme active center only after it has passed into the solution rather than immediately from the adenine nucleotide carrier.

Adenine Nucleotides↗
PubMed2000

Uncoupling effect of anacardic acids from cashew nut shell oil on oxidative phosphorylation of rat liver mitochondria.

Anacardic acids are one of natural products found in not only the cashew nut shell oil but also the nut and fruit juice. The present study was conducted to investigate the uncoupling effect of anacardic acids on oxidative phosphorylation of rat liver mitochondria using succinate (plus rotenone) as a substrate. Four anacardic acids with C15:0, C15:1, C15:2 or C15:3 as an alkyl side chain exhibited uncoupling effects similar to the classical uncoupler, 2,4-dinitrophenol on ADP/O ratio, state 4 and respiratory control ratio (RCR). Anacardic acid with C15:1 side chain was most effective for uncoupling of these compounds. Salicylic acid, which has no alkyl side chain, exhibited a very weak uncoupling effect on oxidative phosphorylation. When the carboxyl group in anacardic acids was lost converting them to the corresponding cardanols, uncoupling activity dramatically decreased regardless of the number of double bonds in the long alkyl chain. These results suggest that the C15 alkyl side chain as well as the carboxyl group may play an important role in assisting the uncoupling activity of anacardic acids in liver mitochondria of animals. This study provides the first evidence of an uncoupling effect of anacardic acids on liver mitochondria

2,4-Dinitrophenol↗