在这个迷你评论中,我们简要调查了导致呼吸复合物III(CIII或细胞色素bc1)产生活性氧(ROS)的分子过程。特别是,我们讨论了导致在CIII的喹啉氧化(Qo)位点产生超氧化物的“正向”和“反向”电子转移途径,以及影响这些反应的成分。然后,我们描述并比较了产生ROS的细菌(荚膜红杆菌属)突变酶及其与疾病相关的线粒体(人类杂种)对应物的特性。正在研究的突变位于细胞色素b的高度保守的酪氨酸残基(胶囊中的Y302C和人线粒体中的Y278C),该残基位于CIII的喹啉氧化(Qo)位点的中心。细菌和人类线粒体病例的主要发现的相似性,包括CIII的催化活性降低,增强ROS的产生和随之而来的细胞反应和损害,是非凡的。这个案例说明了使用生物学上不同但进化上相关的系统进行并行和互补研究的有用性,如α-蛋白细菌和人线粒体。它促进了我们对CIII功能机制和ROS产生的理解,并强调细菌和线粒体呼吸链的超分子组织的可能重要性(即,呼吸体)及其潜在的疾病相关保护作用。本文是特刊的一部分,标题为:呼吸复合物III和相关的BC复合物。
In this mini review, we briefly survey the molecular processes that lead to reactive oxygen species (ROS) production by the respiratory complex III (CIII or cytochrome bc1). In particular, we discuss the \"forward\" and \"reverse\" electron transfer pathways that lead to superoxide generation at the quinol oxidation (Qo) site of CIII, and the components that affect these reactions. We then describe and compare the properties of a bacterial (Rhodobacter capsulatus) mutant enzyme producing ROS with its mitochondrial (human cybrids) counterpart associated with a disease. The mutation under study is located at a highly conserved tyrosine residue of cytochrome b (Y302C in R. capsulatus and Y278C in human mitochondria) that is at the heart of the quinol oxidation (Qo) site of CIII. Similarities of the major findings of bacterial and human mitochondrial cases, including decreased catalytic activity of CIII, enhanced ROS production and ensuing cellular responses and damages, are remarkable. This
case illustrates the usefulness of undertaking parallel and complementary studies using biologically different yet evolutionarily related systems, such as α-proteobacteria and human mitochondria. It progresses our understanding of CIII mechanism of function and ROS production, and underlines the possible importance of supra-molecular organization of bacterial and mitochondrial respiratory chains (i.e., respirasomes) and their potential disease-associated protective roles. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.