S-nitrosation of mitochondrial complex I depends on its structural conformation.
Nitric oxide is known to cause persistent inhibition of mitochondrial respiration as a result of S-nitrosation of NADH: ubiquinone oxidoreductase (complex I) (Clementi, E., Brown, G. C., Feelisch, M., and Moncada, S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 7631-7636). Little is known about whether such nitrosation occurs in physiological conditions and, if so, what are the possible cellular mechanisms. We have now found that the conformational state (active/deactive transition (Vinogradov, A. D. (1998) Biochim. Biophys. Acta 1364, 169-185)) of mitochondrial complex I is an important factor for the interaction of the enzyme with nitrosothiols and peroxynitrite. Only the deactivated, idle form of complex I was susceptible to inhibition by nitrosothiols and peroxynitrite. In contrast, the active form of the enzyme was insensitive to such treatment. Neither form of complex I was inhibited by nitric oxide itself. Our data suggest that the process of active/deactive transition plays an important role in the regulation of complex I activity and cellular respiration by nitric oxide. The implications of this finding for hypoxic or pathophysiological conditions in vivo are discussed.
Galkin
Alexander
A
Wolfson Institute for Biomedical Research, University College London, London, UK. a.galkin@ucl.ac.uk
Moncada
Salvador
S
D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000378:metabolism*; D000860:Hypoxia; D008929:Mitochondria, Heart / Q000378:metabolism*; D008954:Models, Biological; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000737:chemistry; D009206:Myocardium / Q000378:metabolism; D009243:NAD / Q000737:chemistry; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry; D013997:Time Factors
D009097:Multienzyme Complexes; D013438:Sulfhydryl Compounds; D009243:NAD; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I