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. 1996 Apr 1;315(Pt 1):295–299. doi: 10.1042/bj3150295

Rapid reduction of nitric oxide by mitochondria, and reversible inhibition of mitochondrial respiration by nitric oxide.

V Borutaité 1, G C Brown 1
PMCID: PMC1217185  PMID: 8670121

Abstract

Nitric oxide (NO) inhibited the respiration rate of mitochondria isolated from rat heart at sub-micromolar concentrations of NO. The inhibition was rapidly and completely reversible, indicating that NO does not damage mitochondria. The sensitivity of respiration to NO depended on the oxygen concentration, substrate type and respiratory state of the mitochondria, consistent with NO competing with oxygen at cytochrome oxidase. Mitochondria catalysed a rapid rate of NO breakdown, which was greater in the absence of oxygen and was partly inhibited by cyanide and azide, suggesting that at least part of the NO breakdown was due to reduction of NO by cytochrome oxidase. The rapid rate of this breakdown suggests that mitochondrial breakdown of NO may be significant physiologically.

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Selected References

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  1. Balligand J. L., Kelly R. A., Marsden P. A., Smith T. W., Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):347–351. doi: 10.1073/pnas.90.1.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balligand J. L., Kobzik L., Han X., Kaye D. M., Belhassen L., O'Hara D. S., Kelly R. A., Smith T. W., Michel T. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J Biol Chem. 1995 Jun 16;270(24):14582–14586. doi: 10.1074/jbc.270.24.14582. [DOI] [PubMed] [Google Scholar]
  3. Barry W. H. Mechanisms of immune-mediated myocyte injury. Circulation. 1994 May;89(5):2421–2432. doi: 10.1161/01.cir.89.5.2421. [DOI] [PubMed] [Google Scholar]
  4. Bredt D. S., Snyder S. H. Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem. 1994;63:175–195. doi: 10.1146/annurev.bi.63.070194.001135. [DOI] [PubMed] [Google Scholar]
  5. Brown G. C., Bolaños J. P., Heales S. J., Clark J. B. Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration. Neurosci Lett. 1995 Jul 7;193(3):201–204. doi: 10.1016/0304-3940(95)11703-y. [DOI] [PubMed] [Google Scholar]
  6. Brown G. C., Cooper C. E. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett. 1994 Dec 19;356(2-3):295–298. doi: 10.1016/0014-5793(94)01290-3. [DOI] [PubMed] [Google Scholar]
  7. Brown G. C. Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase. FEBS Lett. 1995 Aug 7;369(2-3):136–139. doi: 10.1016/0014-5793(95)00763-y. [DOI] [PubMed] [Google Scholar]
  8. Brown G. C. Reversible binding and inhibition of catalase by nitric oxide. Eur J Biochem. 1995 Aug 15;232(1):188–191. doi: 10.1111/j.1432-1033.1995.tb20798.x. [DOI] [PubMed] [Google Scholar]
  9. Brudvig G. W., Stevens T. H., Chan S. I. Reactions of nitric oxide with cytochrome c oxidase. Biochemistry. 1980 Nov 11;19(23):5275–5285. doi: 10.1021/bi00564a020. [DOI] [PubMed] [Google Scholar]
  10. Clarkson R. B., Norby S. W., Smirnov A., Boyer S., Vahidi N., Nims R. W., Wink D. A. Direct measurement of the accumulation and mitochondrial conversion of nitric oxide within Chinese hamster ovary cells using an intracellular electron paramagnetic resonance technique. Biochim Biophys Acta. 1995 Apr 13;1243(3):496–502. doi: 10.1016/0304-4165(94)00181-v. [DOI] [PubMed] [Google Scholar]
  11. Cleeter M. W., Cooper J. M., Darley-Usmar V. M., Moncada S., Schapira A. H. Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett. 1994 May 23;345(1):50–54. doi: 10.1016/0014-5793(94)00424-2. [DOI] [PubMed] [Google Scholar]
  12. Cooper C. E., Brown G. C. The interactions between nitric oxide and brain nerve terminals as studied by electron paramagnetic resonance. Biochem Biophys Res Commun. 1995 Jul 17;212(2):404–412. doi: 10.1006/bbrc.1995.1984. [DOI] [PubMed] [Google Scholar]
  13. Finkel M. S., Oddis C. V., Jacob T. D., Watkins S. C., Hattler B. G., Simmons R. L. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992 Jul 17;257(5068):387–389. doi: 10.1126/science.1631560. [DOI] [PubMed] [Google Scholar]
  14. Groen A. K., Wanders R. J., Westerhoff H. V., van der Meer R., Tager J. M. Quantification of the contribution of various steps to the control of mitochondrial respiration. J Biol Chem. 1982 Mar 25;257(6):2754–2757. [PubMed] [Google Scholar]
  15. Hare J. M., Keaney J. F., Jr, Balligand J. L., Loscalzo J., Smith T. W., Colucci W. S. Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs. J Clin Invest. 1995 Jan;95(1):360–366. doi: 10.1172/JCI117664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kelm M., Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res. 1990 Jun;66(6):1561–1575. doi: 10.1161/01.res.66.6.1561. [DOI] [PubMed] [Google Scholar]
  17. Knowles R. G., Moncada S. Nitric oxide as a signal in blood vessels. Trends Biochem Sci. 1992 Oct;17(10):399–402. doi: 10.1016/0968-0004(92)90008-w. [DOI] [PubMed] [Google Scholar]
  18. Kobzik L., Reid M. B., Bredt D. S., Stamler J. S. Nitric oxide in skeletal muscle. Nature. 1994 Dec 8;372(6506):546–548. doi: 10.1038/372546a0. [DOI] [PubMed] [Google Scholar]
  19. Kobzik L., Stringer B., Balligand J. L., Reid M. B., Stamler J. S. Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships. Biochem Biophys Res Commun. 1995 Jun 15;211(2):375–381. doi: 10.1006/bbrc.1995.1824. [DOI] [PubMed] [Google Scholar]
  20. Matheis G., Sherman M. P., Buckberg G. D., Haybron D. M., Young H. H., Ignarro L. J. Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury. Am J Physiol. 1992 Feb;262(2 Pt 2):H616–H620. doi: 10.1152/ajpheart.1992.262.2.H616. [DOI] [PubMed] [Google Scholar]
  21. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002–2012. doi: 10.1056/NEJM199312303292706. [DOI] [PubMed] [Google Scholar]
  22. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  23. Richter C., Gogvadze V., Schlapbach R., Schweizer M., Schlegel J. Nitric oxide kills hepatocytes by mobilizing mitochondrial calcium. Biochem Biophys Res Commun. 1994 Dec 15;205(2):1143–1150. doi: 10.1006/bbrc.1994.2785. [DOI] [PubMed] [Google Scholar]
  24. Saraste M., Castresana J. Cytochrome oxidase evolved by tinkering with denitrification enzymes. FEBS Lett. 1994 Mar 14;341(1):1–4. doi: 10.1016/0014-5793(94)80228-9. [DOI] [PubMed] [Google Scholar]
  25. Scholte H. R., Weijers P. J., Wit-Peeters E. M. The localization of mitochondrial creatine kinase, and its use for the determination of the sidedness of submitochondrial particles. Biochim Biophys Acta. 1973 Feb 16;291(3):764–773. doi: 10.1016/0005-2736(73)90479-3. [DOI] [PubMed] [Google Scholar]
  26. Schweizer M., Richter C. Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension. Biochem Biophys Res Commun. 1994 Oct 14;204(1):169–175. doi: 10.1006/bbrc.1994.2441. [DOI] [PubMed] [Google Scholar]

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