Generation of reactive oxygen species by the mitochondrial electron transport chain
Generation of reactive oxygen species by the mitochondrial electron transport chain
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DOI：
10.1046/j.0022-3042.2002.00744.x
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发表时间：
2002-03-01
影响因子：
4.7
通讯作者：
Schubert, D
中科院分区：
文献类型：
--
作者：
Liu, YB;Fiskum, G;Schubert, D
由线粒体电子传递链（ETC）产生的活性氧（ROS）被认为在衰老过程和神经退行性疾病（如帕金森病）的发病机制中是重要的，所述线粒体电子传递链（ETC）由称为复合物I-IV的四种多蛋白复合物组成。先前的研究已经确定了复合物III的泛醌和复合物I的未知组分作为ROS产生的主要位点。在这里，我们表明，生理相关的ROS生成支持的复合物11底物琥珀酸发生在黄素单胞苷脂组（FMN）的复合物I通过反向电子转移，而不是在泛醌的复合物III，因为通常认为。间接证据表明，未知的ROS生成网站内复杂的I也可能是FMN组。因此，这表明，在线粒体中的主要生理和病理相关的ROS生成网站是有限的复合物I的FMN组。这些新的见解阐明了干预线粒体ROS相关过程或疾病的难以捉摸的目标。
Generation of reactive oxygen species (ROS) by the mitochondrial electron transport chain (ETC), which is composed of four multiprotein complexes named complex I-IV, is believed to be important in the aging process and in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. Previous studies have identified the ubiquinone of complex III and an unknown component of complex I as the major sites of ROS generation. Here we show that the physiologically relevant ROS generation supported by the complex 11 substrate succinate occurs at the flavin mononucleotide group (FMN) of complex I through reversed electron transfer, not at the ubiquinone of complex III as commonly believed. Indirect evidence indicates that the unknown ROS-generating site within complex I is also likely to be the FMN group. It is therefore suggested that the major physiologically and pathologically relevant ROS-generating site in mitochondria is limited to the FMN group of complex I. These new insights clarify an elusive target for intervening mitochondrial ROS-related processes or diseases.