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. 1983 Oct;80(19):5807–5811. doi: 10.1073/pnas.80.19.5807

Reversible uncoupling of oxidative phosphorylation at low oxygen tension.

R S Kramer, R D Pearlstein
PMCID: PMC390164  PMID: 6577456

Abstract

The stoichiometry of oxidative phosphorylation at low oxygen tension (less than 3 torr; O2 less than 5 microM) has been measured in rat liver mitochondria. In a steady-state model in which respiration rate was experimentally controlled by either oxygen or substrate (succinate) limitation, flux-dependent variation in the phosphorylation efficiency (P/O ratio) of stimulated mitochondrial respiration was evaluated. P/O ratio remained constant over a wide range of respiration rates in mitochondria limited only by substrate availability. In contrast, oxygen-limited mitochondria demonstrated a continuous decline in P/O ratio as respiration was increasingly restricted. Significant differences in the two test conditions were demonstrated throughout the range of analysis. The effect of oxygen limitation on phosphorylation efficiency was shown to be completely reversed by restoring zero-order kinetics associated with high oxygen tension. These findings are discussed in regard to a proposed uncoupling of mitochondrial coupling site II at low oxygen tension arising as a consequence of energy-dissipating electron flux through the ubiquinone-cytochrome b-c1 region of the respiratory chain (complex III).

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chance B. The nature of electron transfer and energy coupling reactions. FEBS Lett. 1972 Jun 1;23(1):3–20. doi: 10.1016/0014-5793(72)80272-2. [DOI] [PubMed] [Google Scholar]
  2. Degn H., Wohlrab H. Measurement of steady-state values of respiration rate and oxidation levels of respiratory pigments at low oxygen tensions. A new technique. Biochim Biophys Acta. 1971 Sep 7;245(2):347–355. doi: 10.1016/0005-2728(71)90153-8. [DOI] [PubMed] [Google Scholar]
  3. Duffy T. E., Nelson S. R., Lowry O. H. Cerebral carbohydrate metabolism during acute hypoxia and recovery. J Neurochem. 1972 Apr;19(4):959–977. doi: 10.1111/j.1471-4159.1972.tb01417.x. [DOI] [PubMed] [Google Scholar]
  4. Fridovich I. The biology of oxygen radicals. Science. 1978 Sep 8;201(4359):875–880. doi: 10.1126/science.210504. [DOI] [PubMed] [Google Scholar]
  5. Hanstein W. G. Uncoupling of oxidative phosphorylation. Biochim Biophys Acta. 1976 Sep 27;456(2):129–148. doi: 10.1016/0304-4173(76)90010-0. [DOI] [PubMed] [Google Scholar]
  6. Heytler P. G. Uncouplers of oxidative phosphorylation. Pharmacol Ther. 1980;10(3):461–472. doi: 10.1016/0163-7258(80)90027-3. [DOI] [PubMed] [Google Scholar]
  7. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  8. Melnick R. L., Rubenstein C. P., Motzkin S. M. Measurement of mitochondrial oxidative phosphorylation: selective inhibition of adenylate kinase activity by P1,P5-di-(adenosine-5')-pentaphosphate. Anal Biochem. 1979 Jul 1;96(1):7–11. doi: 10.1016/0003-2697(79)90546-3. [DOI] [PubMed] [Google Scholar]
  9. Metzger H., Heuber S. Local oxygen tension and spike activity of the cerebral grey matter of the rat and its response to short intervals of O2 deficiency or CO2 excess. Pflugers Arch. 1977 Aug 29;370(2):201–209. doi: 10.1007/BF00581695. [DOI] [PubMed] [Google Scholar]
  10. Mitchell P. Protonmotive redox mechanism of the cytochrome b-c1 complex in the respiratory chain: protonmotive ubiquinone cycle. FEBS Lett. 1975 Aug 1;56(1):1–6. doi: 10.1016/0014-5793(75)80098-6. [DOI] [PubMed] [Google Scholar]
  11. Norling B., Nelson B. D., Nordenbrand K., Ernster L. Evidence for the occurrence in submitochondrial particles of a dual respiratory chain containing different forms of cytochrome b. Biochim Biophys Acta. 1972 Jul 12;275(1):18–32. doi: 10.1016/0005-2728(72)90021-7. [DOI] [PubMed] [Google Scholar]
  12. SLATER E. C. Phosphorylation coupled with the oxidation of alpha-ketoglutarate by heart-muscle sarcosomes. 3. Experiments with ferricytochrome c as hydrogen acceptor. Biochem J. 1955 Mar;59(3):392–405. doi: 10.1042/bj0590392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Siesjö B. K., Nilsson L. The influence of arterial hypoxemia upon labile phosphates and upon extracellular and intracellular lactate and pyruvate concentrations in the rat brain. Scand J Clin Lab Invest. 1971 Feb;27(1):83–96. doi: 10.3109/00365517109080193. [DOI] [PubMed] [Google Scholar]
  14. Sugano T., Oshino N., Chance B. Mitochondrial functions under hypoxic conditions. The steady states of cytochrome c reduction and of energy metabolism. Biochim Biophys Acta. 1974 Jun 28;347(3):340–358. doi: 10.1016/0005-2728(74)90074-7. [DOI] [PubMed] [Google Scholar]
  15. Trumpower B. L. Function of the iron-sulfur protein of the cytochrome b-c1 segment in electron-transfer and energy-conserving reactions of the mitochondrial respiratory chain. Biochim Biophys Acta. 1981 Dec 4;639(2):129–155. doi: 10.1016/0304-4173(81)90008-2. [DOI] [PubMed] [Google Scholar]
  16. Van der Meer R., Westeroff H. V., Van Dam K. Linear relation between rate and thermodynamic force in enzyme-catalyzed reactions. Biochim Biophys Acta. 1980 Jul 8;591(2):488–493. doi: 10.1016/0005-2728(80)90179-6. [DOI] [PubMed] [Google Scholar]
  17. WEINBACH E. C. A procedure for isolating stable mitochondria from rat liver and kidney. Anal Biochem. 1961 Aug;2:335–343. doi: 10.1016/0003-2697(61)90006-9. [DOI] [PubMed] [Google Scholar]
  18. Walz D. Thermodynamics of oxidation-reduction reactions and its application to bioenergetics. Biochim Biophys Acta. 1979 Mar 14;505(3-4):279–353. doi: 10.1016/0304-4173(79)90007-7. [DOI] [PubMed] [Google Scholar]
  19. Wilson D. F., Erecińska M., Drown C., Silver I. A. The oxygen dependence of cellular energy metabolism. Arch Biochem Biophys. 1979 Jul;195(2):485–493. doi: 10.1016/0003-9861(79)90375-8. [DOI] [PubMed] [Google Scholar]
  20. Ziem-Hanck U., Heber U. Oxygen requirement of photosynthetic CO2 assimilation. Biochim Biophys Acta. 1980 Jul 8;591(2):266–274. doi: 10.1016/0005-2728(80)90158-9. [DOI] [PubMed] [Google Scholar]

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