Research journey of respirasome

Abstract

Respirasome, as a vital part of the oxidative phosphorylation system, undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons. Copious research has been carried out on this lynchpin of respiration. From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I 1 III 2 IV 1 , scientists have gradually uncovered the mysterious veil of the electron transport chain (ETC). With the discovery of the mammalian respiratory mega complex I 2 III 2 IV 2 , a new perspective emerges in the research field of the ETC. Behind these advances glitters the light of the revolution in both theory and technology. Here, we give a short review about how scientists 'see' the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.

Insights into the Roles of the Sideroflexins/SLC56 Family in Iron Homeostasis and Iron-Sulfur Biogenesis

“…Oxidative Phosphorylation (OXPHOS) couples the transport of electrons (through a series of mitochondrial respiratory complexes containing redox-active prosthetic groups) to the production of ATP by the mitochondrial ATP synthase, commonly referred to as the complex V of the respiratory chain ( Figure 3 ). Respiratory complexes (RC) are arranged in supercomplexes (SC) and megacomplexes in the inner mitochondrial membrane [ 35 , 36 ]. The Electron Transport Chain (ETC) comprises four RCs (Complex I-IV) containing more than 70 nuclear DNA encoded subunits and 13 mitochondrial DNA (mtDNA) encoded subunits, some of which include iron-sulfur clusters (ISCs) or heme; those iron-containing groups are essential cofactors for electron transport from one complex to another [ 37 , 38 ].…”

“…The Electron Transport Chain (ETC) comprises four RCs (Complex I-IV) containing more than 70 nuclear DNA encoded subunits and 13 mitochondrial DNA (mtDNA) encoded subunits, some of which include iron-sulfur clusters (ISCs) or heme; those iron-containing groups are essential cofactors for electron transport from one complex to another [ 37 , 38 ]. The purpose of this review is not to give an extensive overview of the abundant literature on RC, so we invite the reader to refer to recent reviews for details on the composition, structure and biogenesis of RC [ 35 , 38 , 39 ].…”

“…The Electron Transport Chain (ETC) comprises four RCs (Complex I-IV) containing more than 70 nuclear DNA encoded subunits and 13 mitochondrial DNA (mtDNA) encoded subunits, some of which include iron-sulfur clusters (ISCs) or heme; those iron-containing groups are essential cofactors for electron transport from one complex to another [37,38]. The purpose of this review is not to give an extensive overview of the abundant literature on RC, so we invite the reader to refer to recent reviews for details on the composition, structure and biogenesis of RC [35,38,39]. Mammalian Complex II, the smallest of the RC, is composed of only four subunits: succinate dehydrogenase [ubiquinone] flavoprotein (also known as Flavoprotein subunit of complex II, Fp, SDHA), succinate dehydrogenase [ubiquinone] iron-sulfur subunit (a Fe-S protein also named Ip or SDHB), the membrane-anchoring succinate dehydrogenase cytochrome b560 subunit (CybL, SDHC), and finally the succinate dehydrogenase (ubiquinone) cytochrome b small subunit (CybS, SDHD).…”

Regulation of Cytochrome c Oxidase by Natural Compounds Resveratrol, (–)-Epicatechin, and Betaine

“…During electron transfer, complexes I, III, and IV (also known as cytochrome c oxidase; COX) pump protons across the inner mitochondrial membrane and create the mitochondrial membrane potential which is utilized by ATP synthase to produce ATP from ADP and P i . The OXPHOS complexes are also proposed to play a crucial role in maintaining cristae morphology, folded structures of the inner mitochondrial membrane [2]. In many species and tissues, the ETC complexes form supercomplexes with various stoichiometries, with respirasome (CI 1 CIII 2 CIV 1 ) being the most well-known [2].…”

“…The OXPHOS complexes are also proposed to play a crucial role in maintaining cristae morphology, folded structures of the inner mitochondrial membrane [2]. In many species and tissues, the ETC complexes form supercomplexes with various stoichiometries, with respirasome (CI 1 CIII 2 CIV 1 ) being the most well-known [2]. The significance of these supramolecular structures has been suggested to be functionally relevant to ETC activity by increasing the efficiency of NAD-linked respiration and by reducing ROS production [3].…”