7o37
Murine supercomplex CIII2CIV in the assembled locked conformation
Structural highlights
FunctionQCR1_MOUSE Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (By similarity). The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties. May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III (By similarity). Seems to play an important role in the maintenance of proper mitochondrial function in nigral dopaminergic neurons (By similarity).[UniProtKB:P07256][UniProtKB:P31800][UniProtKB:P31930] Publication Abstract from PubMedThe enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes(1), whose precise role is debated. Supercomplexes CIII(2)CIV(1-2) (refs. (2,3)), CICIII(2) (ref. (4)) and CICIII(2)CIV (respirasome)(5-10) exist in mammals, but in contrast to CICIII(2) and the respirasome, to date the only known eukaryotic structures of CIII(2)CIV(1-2) come from Saccharomyces cerevisiae(11,12) and plants(13), which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIII(2)CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII(2)CIV from the CIII(2) precursor to the final CIII(2)CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. (14)) deep into CIII(2), while its C terminus is integrated into CIV. Our structures (which include CICIII(2) and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII(2)CIV and has no role in the assembly of the respirasome. We show that CIII(2) is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII(2), explaining the presence of one copy of CIV in CIII(2)CIV in mammals. Finally, we show that CIII(2) and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII(2)CIV in fine tuning the efficiency of electron transfer in the electron transport chain. Structure and assembly of the mammalian mitochondrial supercomplex CIII(2)CIV.,Vercellino I, Sazanov LA Nature. 2021 Oct;598(7880):364-367. doi: 10.1038/s41586-021-03927-z. Epub 2021 , Oct 6. PMID:34616041[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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