Grivennikova Vera G, Gladyshev Grigory V, Zharova Tatyana V, Borisov Vitaliy B
Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory, 119991 Moscow, Russia.
Int J Mol Sci. 2024 Dec 14;25(24):13421. doi: 10.3390/ijms252413421.
Proton-translocating NADH-ubiquinone oxidoreductase (complex I) catalyzes the oxidation of NADH by ubiquinone accompanied by the transmembrane transfer of four protons, thus contributing to the formation of a proton motive force () across the coupling membranes of mitochondria and bacteria, which drives ATP synthesis in oxidative phosphorylation. In recent years, great progress has been achieved in resolving complex I structure by means of X-ray crystallography and high-resolution cryo-electron microscopy, which has led to the formulation of detailed hypotheses concerning the molecular mechanism of coupling of the redox reaction to vectorial proton translocation. To test and probe proposed mechanisms, a comprehensive study of complex I using other methods including molecular dynamics and a variety of biochemical studies such as kinetic and inhibitory analysis is required. Due to complex I being a major electron entry point for oxidative metabolism, various mutations of the enzyme lead to the development of severe pathologies and/or are associated with human metabolic disorders and have been well documented. This review examines current information on the structure and subunit composition of complex I of eukaryotes and prokaryotes, reactions catalyzed by this enzyme, and ways to regulate them. The review also discusses biomedical aspects related to the enzyme in light of recent findings.
质子转运型NADH-泛醌氧化还原酶（复合体I）催化NADH被泛醌氧化，同时伴有四个质子的跨膜转移，从而有助于在线粒体和细菌的偶联膜上形成质子动力势（），驱动氧化磷酸化过程中的ATP合成。近年来，通过X射线晶体学和高分辨率冷冻电子显微镜在解析复合体I结构方面取得了巨大进展，这使得关于氧化还原反应与向量质子转运偶联的分子机制的详细假说得以形成。为了测试和探究所提出的机制，需要使用包括分子动力学在内的其他方法以及各种生化研究（如动力学和抑制分析）对复合体I进行全面研究。由于复合体I是氧化代谢的主要电子进入点，该酶的各种突变会导致严重疾病的发生和/或与人类代谢紊乱相关，并且已有充分记录。本综述考察了有关真核生物和原核生物复合体I的结构和亚基组成、该酶催化的反应以及调节这些反应的方式的当前信息。本综述还根据最近的研究结果讨论了与该酶相关的生物医学方面。
