期刊
NATURE
卷 598, 期 7880, 页码 364-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03927-z
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资金
- European Union [754411]
The enzymes of the mitochondrial electron transport chain play a vital role in cell metabolism, forming supercomplexes in vivo. The assembly factor SCAF1 is crucial in mediating the assembly of CIII2CIV, but not involved in the assembly of the respirasome. Assembling into supercomplexes enhances the catalytic efficiency of CIII2 and CIV, potentially fine tuning the electron transfer efficiency in the electron transport chain.
The 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 CIII2CIV1-2 (refs.(2,3)), CICIII2 (ref.(4)) and CICIII2CIV (respirasome)(5-10) exist in mammals, but in contrast to CICIII2 and the respirasome, to date the only known eukaryotic structures of CIII2CIV1-2 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) CIII2CIV and its assembly intermediates, in different conformations. We describe the assembly of CIII2CIV from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref.(14)) deep into CIII2, while its C terminus is integrated into CIV. Our structures (which include CICIII2 and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2 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 CIII2, explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer in the electron transport chain.
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