Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation.
Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation.
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DOI：
10.1089/ars.2009.2743
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发表时间：
2010-06-15
影响因子：
6.6
通讯作者：
Willems, Peter H G M
中科院分区：
文献类型：
--
作者：
Koopman, Werner J H;Nijtmans, Leo G J;Willems, Peter H G M
事实上，每个哺乳动物细胞都含有线粒体。这些双膜细胞器不断改变形状和位置，并包含丙酮酸，脂肪酸和氨基酸氧化转化为ATP的完整代谢机制。线粒体在细胞内Ca 2+和氧化还原稳态以及细胞凋亡诱导中起关键作用。线粒体功能和完整性的维持需要跨线粒体内膜的内部负电位差。这种电势由电子传输链（ETC）维持。NADH：泛醌氧化还原酶或复合物I（Cl），ETC的第一个和最大的蛋白质复合物，将NADH的氧化与泛醌的还原偶联。在此过程中，电子可从Cl逸出并与环境氧反应以产生超氧化物和衍生的活性氧物质（ROS）。取决于它们的产生和抗氧化系统的清除之间的平衡，ROS可以作为信号分子或诱导对各种生物分子的损伤或两者兼而有之。后者最终导致线粒体和细胞功能和完整性的丧失。在这篇综述中，我们讨论了（a）CI在线粒体功能中的作用;（B）CI的组成、结构和生物起源;（c）CI功能的调节;（d）CI在ROS产生中的作用;（e）CI缺乏的适应性反应。
Virtually every mammalian cell contains mitochondria. These double-membrane organelles continuously change shape and position and contain the complete metabolic machinery for the oxidative conversion of pyruvate, fatty acids, and amino acids into ATP. Mitochondria are crucially involved in cellular Ca2+ and redox homeostasis and apoptosis induction. Maintenance of mitochondrial function and integrity requires an inside-negative potential difference across the mitochondrial inner membrane. This potential is sustained by the electron-transport chain (ETC). NADH:ubiquinone oxidoreductase or complex I (CI), the first and largest protein complex of the ETC, couples the oxidation of NADH to the reduction of ubiquinone. During this process, electrons can escape from CI and react with ambient oxygen to produce superoxide and derived reactive oxygen species (ROS). Depending on the balance between their production and removal by antioxidant systems, ROS may function as signaling molecules or induce damage to a variety of biomolecules or both. The latter ultimately leads to a loss of mitochondrial and cellular function and integrity. In this review, we discuss (a) the role of CI in mitochondrial functioning; (b) the composition, structure, and biogenesis of CI; (c) regulation of CI function; (d) the role of CI in ROS generation; and (e) adaptive responses to CI deficiency.