S-nitrosation of mitochondrial complex I depends on its structural conformation

Alexander Galkin, Salvador Moncada

    Research output: Contribution to journalArticlepeer-review


    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. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
    Original languageEnglish
    Pages (from-to)37448-37453
    Number of pages5
    JournalJournal of Biological Chemistry
    Issue number52
    Publication statusPublished - 28 Dec 2007


    • Animals
    • Anoxia
    • Cattle
    • Electron Transport Complex I/*metabolism
    • Mitochondria, Heart/*metabolism
    • Models, Biological
    • Molecular Conformation
    • Multienzyme Complexes/chemistry
    • Myocardium/metabolism
    • NAD/chemistry
    • NADH, NADPH Oxidoreductases/chemistry
    • Nitric Oxide/chemistry
    • Oxidative Stress
    • Peroxynitrous Acid/chemistry
    • Sulfhydryl Compounds/chemistry
    • Superoxides/chemistry
    • Time Factors


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