PDF《线粒体呼吸链与活性氧》

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

520 生命科学 第20 卷 线粒体是真核生物细胞中特别重要的细胞器, 已有一个多世纪的研究历史[1] .在生命进化渊源 上,它来源于 内共生 的好氧古细菌,用自己 的遗传基因(mtDNA)编码线粒体氧化磷酸化酶复合 体的关键亚基以控制 ATP合成;

在为生命供能供热 的同时,还产生活性氧(ROS)作为细胞氧化还原电 势和 Redox 信号的原发因子.ROS 对氧化应激、细 胞凋亡、基因表达等重要细胞过程的调控有重要作 用,是生命科学和分子医学当前最活跃的前沿领域 之一[2] .由于线粒体的 ATP 合成和 ROS生成两者的 动态平衡和消长调控对决定生物的生存、发育、衰老、疾病和死亡有关键意义[3-5] .本文讨论的主要 问题是线粒体 ROS 的产生、转移及其代谢调控等.

1 线粒体呼吸链是生物活性氧(ROS)最主要来源 线粒体呼吸产生的ROS主要是指O2的单电子还 原产物,超氧阴离子(O2 - ・)及其衍生的 HO2・、H2O

2、 OH・ 和单线态氧1 O2 等.已知,生物体中有多种酶 系可将 O2 转变为 O2 - ・.除线粒体外,尚包括质膜的 NADPH 氧化酶和胞浆细胞色素P450 氧还酶,Xan- thine Oxidase 以及其他细胞器中的酶系[6] .最新报 道线粒体内外膜间的氧还蛋白 p66SHc ,通过氧化细 胞色素 C 来利用呼吸链的还原当量产生 H2O2,是线 粒体呼吸链 ROS 生成的新途径[7] .在线粒体中,除 内膜呼吸链酶系,也包括其外膜中的 cytochrome b5 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-p66shc 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 descriptions for its mode of action are controversial. A very interesting Uncoupling double-loop of H+ and O2 - ・ cycling model was postulated to combine and integrate different models concerning the mechanisms of superoxide activation and translocation across mitochondrial membranes indicating the central role of HO2・ fromed from intereaction of both H+ and O2 - ・ cycling in connection with FFA shuttling model and UCPs activation model ;