Richter C, Gogvadze V, Laffranchi R, Schlapbach R, Schweizer M, Suter M, Walter P, Yaffee M
Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Zürich.
Biochim Biophys Acta. 1995 May 24;1271(1):67-74. doi: 10.1016/0925-4439(95)00012-s.
Reactive oxygen species (ROS: superoxide radical, O2.-; hydrogen peroxide, H2O2; hydroxyl radical, OH.), which arise from the univalent reduction of dioxygen are formed in mitochondria. We summarize here results which indicate that ROS, and also the radical nitrogen monoxide ('nitric oxide', NO), act as physiological modulators of some mitochondrial functions, but may also damage mitochondria. Hydrogen peroxide, which originates in mitochondria predominantly from the dismutation of superoxide, causes oxidation of mitochondrial pyridine nucleotides and thereby stimulates a specific Ca2+ release from intact mitochondria. This release is prevented by cyclosporin A (CSA). Hydrogen peroxide thus contributes to the maintenance of cellular Ca2+ homeostasis. A stimulation of mitochondrial ROS production followed by an enhanced Ca2+ release and re uptake (Ca2+ 'cycling') by mitochondria causes apoptosis and necrosis, and contributes to hypoxia/reperfusion injury. These kinds of cell injury can be attenuated at the mitochondrial level by CSA. When ROS are produced in excessive amounts in mitochondria nucleic acids, proteins, and lipids are extensively modified by oxidation. Physiological (sub-micromolar) concentrations of NO potently and reversibly deenergize mitochondria at oxygen tensions that prevail in cells by transiently binding to cytochrome oxidase. This is paralleled by mitochondrial Ca2+ release and uptake. Higher NO concentrations or prolonged exposure of cells to NO causes their death. It is concluded that ROS and NO are important physiological reactants in mitochondria and become toxic only when present in excessive amounts.
活性氧（ROS：超氧阴离子自由基，O2.-；过氧化氢，H2O2；羟基自由基，OH.）由线粒体中氧的单价还原产生。我们在此总结的结果表明，ROS以及自由基一氧化氮（“一氧化氮”，NO）可作为某些线粒体功能的生理调节剂，但也可能损害线粒体。过氧化氢主要在线粒体中由超氧阴离子的歧化产生，它会导致线粒体吡啶核苷酸的氧化，从而刺激完整线粒体释放特定的Ca2+。这种释放可被环孢菌素A（CSA）阻止。因此，过氧化氢有助于维持细胞内Ca2+稳态。线粒体ROS产生的刺激随后导致线粒体Ca2+释放和再摄取（Ca2+“循环”）增强，从而导致细胞凋亡和坏死，并导致缺氧/再灌注损伤。这些类型的细胞损伤可通过CSA在线粒体水平上减轻。当线粒体中产生过量的ROS时，核酸、蛋白质和脂质会被广泛氧化修饰。生理浓度（亚微摩尔）的NO在细胞中普遍存在的氧张力下，通过与细胞色素氧化酶短暂结合，有力且可逆地使线粒体失去能量。这与线粒体Ca2+的释放和摄取同时发生。较高浓度的NO或细胞长时间暴露于NO会导致细胞死亡。结论是，ROS和NO是线粒体中的重要生理反应物，只有在过量存在时才会变得有毒。
