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-Structure paper
Title | Resting mitochondrial complex I from adopts a helix-locked state. |
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Journal, issue, pages | Elife, Vol. 12, Year 2023 |
Publish date | Mar 23, 2023 |
![]() | Abhilash Padavannil / Anjaneyulu Murari / Shauna-Kay Rhooms / Edward Owusu-Ansah / James A Letts / ![]() |
PubMed Abstract | Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the ...Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can adopt a biochemically defined off-pathway 'deactive' state, whereas complex I from Protostomia cannot. The presence of off-pathway states complicates the interpretation of structural results and has led to considerable mechanistic debate. Here, we report the structure of mitochondrial complex I from the thoracic muscles of the model protostome . We show that although complex I (-CI) does not have a NEM-sensitive deactive state, it does show slow activation kinetics indicative of an off-pathway resting state. The resting-state structure of -CI from the thoracic muscle reveals multiple conformations. We identify a helix-locked state in which an N-terminal α-helix on the NDUFS4 subunit wedges between the peripheral and membrane arms. Comparison of the -CI structure and conformational states to those observed in bacteria, yeast, and mammals provides insight into the roles of subunits across organisms, explains why the -CI off-pathway resting state is NEM insensitive, and raises questions regarding current mechanistic models of complex I turnover. |
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Methods | EM (single particle) |
Resolution | 3.3 - 3.4 Å |
Structure data | EMDB-28581, PDB-8esw: EMDB-28582, PDB-8esz: |
Chemicals | ![]() ChemComp-CDL: ![]() ChemComp-ZN: ![]() ChemComp-SF4: ![]() ChemComp-FES: ![]() ChemComp-PC1: ![]() ChemComp-3PE: ![]() ChemComp-ZMP: ![]() ChemComp-NDP: ![]() ChemComp-FMN: ![]() ChemComp-DGT: ![]() ChemComp-U10: ![]() ChemComp-C14: ![]() ChemComp-OCT: ![]() ChemComp-D12: ![]() ChemComp-WSF: |
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