Galkin Alexander, Moncada Salvador
Wolfson Institute for Biomedical Research, University College London, London, UK.
J Biol Chem. 2007 Dec 28;282(52):37448-53. doi: 10.1074/jbc.M707543200. Epub 2007 Oct 23.
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.
已知一氧化氮会因NADH：泛醌氧化还原酶（复合体I）的S-亚硝基化作用而导致线粒体呼吸的持续抑制（克莱门蒂，E.，布朗，G.C.，费利施，M.，和蒙卡达，S.（1998年）《美国国家科学院院刊》95，7631 - 7636）。关于这种亚硝基化作用是否在生理条件下发生，以及如果发生的话，可能的细胞机制是什么，目前知之甚少。我们现在发现线粒体复合体I的构象状态（活性/非活性转变（维诺格拉多夫，A.D.（1998年）《生物化学与生物物理学报》1364，169 - 185））是该酶与亚硝基硫醇和过氧亚硝酸根相互作用的一个重要因素。只有非活性的、闲置形式的复合体I易受亚硝基硫醇和过氧亚硝酸根的抑制。相反，该酶的活性形式对这种处理不敏感。复合体I的两种形式都不会被一氧化氮本身抑制。我们的数据表明活性/非活性转变过程在一氧化氮对复合体I活性和细胞呼吸的调节中起重要作用。本文讨论了这一发现对体内缺氧或病理生理状况的意义。
