Cardiac mitochondria and reactive oxygen species generation.
Cardiac mitochondria and reactive oxygen species generation.
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DOI：
10.1161/circresaha.114.300559
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发表时间：
2014-01-31
影响因子：
20.1
通讯作者：
Zweier JL
中科院分区：
文献类型：
--
作者：
Chen YR;Zweier JL
线粒体ROS已成为心血管系统疾病和氧化还原信号的重要机制。在基础或病理条件下，ROS产生的电子泄漏主要由电子传输链和由膜电位(ΔΨ)和质子梯度(ΔpH)组成的质子动力调节。控制线粒体ROS产生的几个因素包括：复合体I的FMN和FMN结合域，复合体I的乌双半喹和醌结合域，复合体II的FAD结合部分和醌结合口袋(QP)，以及由复合体III的Q循环介导的不稳定的半喹酮·QO−。在心血管系统中，线粒体ROS参与调节代谢扩张和预适应样的mKATP通道激活的生理效应。此外，谷胱甘肽在复合体I和复合体II中的氧化翻译后修饰已经被证明影响酶催化、蛋白质-蛋白质相互作用和酶介导的ROS的产生。与氧化或亚硝化应激相关的条件，如心肌缺血和再灌流，通过氧化损伤复合体I和II增加线粒体ROS的产生，以及·O2−通过乌头酸酶诱导羟基自由基的产生。进一步深入了解特定的氧化还原翻译后修饰调控线粒体ROS产生的细胞机制，将丰富我们对氧化还原信号转导的理解，并为氧化应激干扰正常氧化还原信号的心血管疾病寻找新的治疗靶点。
Mitochondrial ROS have emerged as an important mechanism of disease and redox signaling in the cardiovascular system. Under basal or pathological conditions, electron leakage for ROS production is primarily mediated by the electron transport chain and proton motive force consisting of a membrane potential (ΔΨ) and a proton gradient (ΔpH). Several factors controlling ROS production in mitochondria include FMN and the FMN-binding domain of complex I, ubisemiquinone and quinone-binding domain of complex I, FAD binding moiety and quinone-binding pocket (Qp) of complex II, and unstable semiquinone •Qo− mediated by the Q cycle of complex III. In mitochondrial complex I, specific cysteinyl redox domains modulate ROS production from the FMN moiety and iron sulfur clusters. In the cardiovascular system, mitochondrial ROS have been linked to mediating physiological effects of metabolic dilation and preconditioning-like mKATP channel activation. Furthermore, oxidative post-translational modification by glutathione in complex I and complex II has been shown to affect enzymatic catalysis, protein-protein interactions, and enzyme-mediated ROS production. Conditions associated with oxidative or nitrosative stress, such as myocardial ischemia and reperfusion, increase mitochondrial ROS production via oxidative injury of complexes I and II, and •O2−-induced hydroxyl radical production by aconitase. Further insight into cellular mechanisms by which specific redox post-translational modifications regulate ROS production in mitochondria will enrich our understanding of redox signal transduction and identify new therapeutic targets for cardiovascular diseases in which oxidative stress perturbs normal redox signaling.