Mitochondrial free radical generation, oxidative stress, and aging
Mitochondrial free radical generation, oxidative stress, and aging
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DOI：
10.1016/s0891-5849(00)00317-8
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发表时间：
2000-08-01
影响因子：
7.4
通讯作者：
Davies, KJA
中科院分区：
文献类型：
--
作者：
Cadenas, E;Davies, KJA
线粒体被描述为“细胞的动力室”，因为它们将电子传递和质子泵出的能量释放活动与氧化磷酸化的能量储存过程联系起来，以ATP的形式利用食物的能量。然而，这样的能量过程并非没有危险，电子传递链已被证明有些“泄漏”。线粒体电子传递链与分子氧的这种副反应直接产生超氧阴离子自由基（O₂⁻·），它歧化形成过氧化氢（H₂O₂），过氧化氢可进一步反应形成羟基自由基（·OH）。除了线粒体内膜的这些有毒的电子传递链反应外，线粒体外膜的单胺氧化酶催化生物胺的氧化脱氨作用，并且是过氧化氢的大量来源，这导致线粒体基质和细胞质中活性物质的稳态浓度增加。在本文中，我们综述了这些活性氧物质的线粒体产生速率和稳态水平。由线粒体产生的或来自细胞内或细胞外其他部位的活性氧物质会对线粒体成分造成损害并引发降解过程。这种毒性反应对衰老过程有重要影响，并构成了“衰老的自由基理论”的核心原则。在本文中，我们综述了目前对氧化应激导致的线粒体DNA、RNA和蛋白质修饰以及核酸酶和蛋白酶对氧化损伤产物的酶促清除的理解。探讨了线粒体氧化多核苷酸和蛋白质周转对细胞凋亡和衰老的可能贡献。（C）2000爱思唯尔科学公司
Mitochondria have been described as "the powerhouses of the cell" because they link the energy-releasing activities of electron transport and proton pumping with the energy conserving process of oxidative phosphorylation, to harness the value of foods in the form of ATP. Such energetic processes are not without dangers, however, and the electron transport chain has proved to be somewhat "leaky." Such side reactions of the mitochondrial electron transport chain with molecular oxygen directly generate the superoxide anion radical(O-2(.-)), which dismutates to form hydrogen peroxide (H2O2), which can further react to form the hydroxyl radical (HO.). In addition to these toxic electron transport chain reactions of the inner mitochondrial membrane. the mitochondrial outer membrane enzyme monoamine oxidase catalyzes the oxidative deamination of biogenic amines and is a quantitatively large source of H2O2 that contributes to an increase in the steady state concentrations of reactive species within both the mitochondrial matrix and cytosol. In this article we review the mitochondrial rates of production and steady state levels of these reactive oxygen species. Reactive oxygen species generated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Such toxic reactions contribute significantly to the aging process and form the central dogma of "The Free Radical Theory of Aging." In this article we review current understandings of mitochondrial DNA, RNA, and protein modifications by oxidative stress and the enzymatic removal of oxidatively damaged products by nucleases and proteases. The possible contributions of mitochondrial oxidative polynucleotide and protein turnover to apoptosis and aging are explored. (C) 2000 Elsevier Science Inc.