Department of Basic Medical Sciences, Neurosciences and Sense Organs (BMSNSO), Section of Medical Biochemistry, University of Bari 'Aldo Moro', Piazza G. Cesare 11, 70124, Bari, Italy.
Institute of Biomembranes and Bioenergetics, National Research Council at BMSNSO, Piazza G. Cesare 11, 70124, Bari, Italy.
Biol Rev Camb Philos Soc. 2018 Feb;93(1):322-349. doi: 10.1111/brv.12347. Epub 2017 Jun 21.
The respiratory chain of mitochondria and bacteria is made up of a set of membrane-associated enzyme complexes which catalyse sequential, stepwise transfer of reducing equivalents from substrates to oxygen and convert redox energy into a transmembrane protonmotive force (PMF) by proton translocation from a negative (N) to a positive (P) aqueous phase separated by the coupling membrane. There are three basic mechanisms by which a membrane-associated redox enzyme can generate a PMF. These are membrane anisotropic arrangement of the primary redox catalysis with: (i) vectorial electron transfer by redox metal centres from the P to the N side of the membrane; (ii) hydrogen transfer by movement of quinones across the membrane, from a reduction site at the N side to an oxidation site at the P side; (iii) a different type of mechanism based on co-operative allosteric linkage between electron transfer at the metal redox centres and transmembrane electrogenic proton translocation by apoproteins. The results of advanced experimental and theoretical analyses and in particular X-ray crystallography show that these three mechanisms contribute differently to the protonmotive activity of cytochrome c oxidase, ubiquinone-cytochrome c oxidoreductase and NADH-ubiquinone oxidoreductase of the respiratory chain. This review considers the main features, recent experimental advances and still unresolved problems in the molecular/atomic mechanism of coupling between the transfer of reducing equivalents and proton translocation in these three protonmotive redox complexes.
线粒体和细菌的呼吸链由一组膜相关的酶复合物组成，这些复合物催化还原当量从底物到氧的顺序逐步转移，并通过质子从负（N）相到正（P）相的跨膜迁移将氧化还原能量转化为跨膜质子动力势（PMF），这两个相由偶联膜隔开。膜相关的氧化还原酶可以通过三种基本机制产生 PMF。这些机制是：（i）通过氧化还原金属中心从膜的 P 侧到 N 侧的向量电子转移；（ii）通过醌在膜内的移动，从 N 侧的还原部位到 P 侧的氧化部位进行氢转移；（iii）一种基于金属氧化还原中心的电子转移与脱辅基蛋白的跨膜生电质子迁移之间的协同变构连接的不同类型的机制。先进的实验和理论分析的结果，特别是 X 射线晶体学表明，这三种机制对呼吸链细胞色素 c 氧化酶、泛醌-细胞色素 c 氧化还原酶和 NADH-泛醌氧化还原酶的质子动力活性有不同的贡献。这篇综述考虑了这三种质子动力氧化还原复合物中还原当量转移和质子跨膜迁移之间偶联的分子/原子机制的主要特征、最近的实验进展和尚未解决的问题。
