线粒体呼吸链与活性氧

已知有氧真核生物细胞吸收的氧分子绝大部分都是在线粒体呼吸链末端细胞色素氧化酶上通过四步单电子还原生成水。但同时也有1％-2％的氧可在呼吸链中途接受单电子或双电子被部分还原生成超氧（O2·^-和过氧化氢（H2O2）作为呼吸作用的正常代谢产物。此种来源于线粒体呼吸链的O2·^-和H2O2不但在多种病理的氧化损伤中起关键作用，同样它们也是正常生理条件下对多种细胞过程具有基本调控意义的氧还信号。基于Chance实验室约自20世纪70到90年代的早期研究贡献以及20世纪90年代后其他各实验室的研究新进展，我们聚焦于下述四个相关问题的评述和讨论：（1）由于线粒体内膜面积及其含有的呼吸链复合体酶活力远远高出细胞中所有膜系数量和相关酶活力之总和，因而线粒体呼吸链产生的O2·^-和H2O2构成生物体内最大数量ROS的恒定来源；（2）线粒体呼吸链复合体III的Q循环中Qo位点中半醌自由基（UQH·）已明确是O2·^-的单电子来源；还原细胞色素C-P66^SHC是生成H2O2的双电子供体。虽然复合体I也是产生线粒体基质内O2·^-的主要来源，但由于其确切生成位点尚未明确，在invivo条件下能否产生大量O2·^-也尚有争议；（3）线粒体呼吸链产生O2·^-后的分配和跨膜转移涉及其生理病理作用机制和作用靶点等复杂而重要的问题，直到目前尚未意见一致。“质子和O2·^-循环双回路解偶联模型”整合了目前提出的几种假说的联系点，指出H^＋和O2·^-相互作用生成HO2·及其跨膜很可能是这一复杂问题的中心环节，并与O2·^-对“脂肪酸shuttling model”或O2·^-对“UCPS激活”模型形成了内在的联系；（4）线粒体呼吸形成的△P（△ψ和△pH）能直接控制呼吸链的ROS生成，并以非线性（非欧姆）相关方式通过影响Q循环中的Qo半醌的氧还态和寿命来调节O2·^-生成的急速?

Mitochondrial respiratory chain and reactive oxygen species

It has been established that most oxygen consumed by aerobic eukaryotic cells is reduced to water through 4 steps of single electron reduction by the terminal cytochrome c oxidase of mitochondrial respiratory chain. Meanwhile, a small proportion （1%-2%） of consumed oxygen can also be reduced partially by one or two electrons in the mid-pathway of respiratory chain to generate superoxide（O2·^-） or hydrogen perioxide（H2O2） as normal metabolic products of oxygen during respiration. As the primary sources of ROS species derived from mitochondrial respiratory chain, both O2·^- and H2O2 have been shown to be more crucial not only in a variety of harmful oxidative damage under pathological conditions, but also to be pivotal significant physiologically in redox signaling for many cellullar events. On the basis of the research achievement from 1970s to 1990s contributed mainly by Chance＇s group and from 1990s to present by several other groups, the following four aspects of this topic were mainly reviewed and discussed in this article, namely, （1） Mitochondrial respiratory chain derived O2·^- and H2o2 serve quantitatively as the most important source of ROS in living body, mainly due to the largest amount of the inner mitochondrial membrane surface and of the enzymes activity of respiratory chain complexes among cellular membrane and enzyme system; （2） O2·^- generating sites in components of respiratory chain have been determined to be ubisemiquinone at Qo site of Q cycle in complex III. Although complex I is another important O2·^- sources of respiratory chain, its precise site（s） has not been established yet. However, the electron sources from respiratory chain to reduce Cyt c-p66^She system have been shown to make H2o2 directly without formation of superoxide; （3） The mechanisms of O2·^- partitioning and translocation across membranes from its generating sites in mitochondria are still not elucidated and charctericized. Although several models have been hypothesized, however, the des