Vercellino 2022 Nat Rev Mol Cell Biol
| Vercellino I, Sazanov LA (2022) The assembly, regulation and function of the mitochondrial respiratory chain. Nat Rev Mol Cell Biol 23:141-161. doi: 10.1038/s41580-021-00415-0 |
Vercellino I, Sazanov Leonid A (2022) Nat Rev Mol Cell Biol
Abstract: The mitochondrial oxidative phosphorylation system is central to cellular metabolism. It comprises five enzymatic complexes and two mobile electron carriers that work in a mitochondrial respiratory chain. By coupling the oxidation of reducing equivalents coming into mitochondria to the generation and subsequent dissipation of a proton gradient across the inner mitochondrial membrane, this electron transport chain drives the production of ATP, which is then used as a primary energy carrier in virtually all cellular processes. Minimal perturbations of the respiratory chain activity are linked to diseases; therefore, it is necessary to understand how these complexes are assembled and regulated and how they function. In this Review, we outline the latest assembly models for each individual complex, and we also highlight the recent discoveries indicating that the formation of larger assemblies, known as respiratory supercomplexes, originates from the association of the intermediates of individual complexes. We then discuss how recent cryo-electron microscopy structures have been key to answering open questions on the function of the electron transport chain in mitochondrial respiration and how supercomplexes and other factors, including metabolites, can regulate the activity of the single complexes. When relevant, we discuss how these mechanisms contribute to physiology and outline their deregulation in human diseases.
• Bioblast editor: Gnaiger E
Selected quotes
- Complex III2 accepts electrons in the form of quinol from both complex I and complex II, which in turn oxidize NADH and succinate, respectively, as well as from several dehydrogenases (dihydroorotate dehydrogenase, electron transfer flavoprotein:ubiquinone oxidoreductase, glycerol 3-phosphate dehydrogenase, choline dehydrogenase, proline dehydrogenase, sulfide:quinone oxidoreductase) also reducing ubiquinone.
- Figure 1: The double arrow emphasizes that complex II (CII) belongs to both the Krebs cycle and the OXPHOS system. The electron carriers NADH, succinate, quinone (Q) and cytochrome c (C) are depicted as yellow ovals. NADH donates electrons to complex I (CI) and succinate donates electrons to complex II (CII), while quinone shuttles electrons from complexes I and II to complex III2 (CIII2) and cytochrome c (cyt c) shuttles electrons from complex III2 to complex IV (CIV).
Labels:
Enzyme: Complex I, Complex III, Complex IV;cytochrome c oxidase, Supercomplex
