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| Title | SCAF1 drives the compositional diversity of mammalian respirasomes. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Year 2024 |
| Publish date | Apr 4, 2024 |
 Authors | Irene Vercellino / Leonid A Sazanov /   |
| PubMed Abstract | Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies ...Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the 'canonical' respirasome (the C-respirasome, CICIIICIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the 'back' of CI, instead of the 'toe'. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions. |
 External links | Nat Struct Mol Biol / PubMed:38575788 |
| Methods | EM (single particle) |
| Resolution | 2.7 - 3.8 Å |
| Structure data | EMDB-17989, PDB-8pw5: EMDB-17990, PDB-8pw6: EMDB-17991, PDB-8pw7:  EMDB-18011: focused map of complex I membrane arm from A respirasome, murine liver  EMDB-18012: focused map of complex I peripheral arm from A respirasome, murine liver  EMDB-18013: focused map of complex III from A prespirasome, murine liver  EMDB-18014: focused map of CIV from A respirasome, murine liver  EMDB-18015: consensus refinement of A respirasome, murine liver  EMDB-18017: focused map of complex I peripheral arm from C respirasome, murine liver  EMDB-18018: focused map of complex I membrane arm from C respirasome, murine liver  EMDB-18019: focused map of complex III from C respirasome, murine liver  EMDB-18020: focused map of complex IV from C respirasome, murine liver  EMDB-18021: global refinement of C respirasome, murine liver  EMDB-18022: focused map of complex I peripheral arm from SC respirasome, murine liver  EMDB-18023: focused map of complex I membrane arm from SC respirasome, murine liver  EMDB-18024: focused map of the canonical CIV from SC respirasome, murine liver  EMDB-18025: focused map of complex III from SC respirasome, murine liver  EMDB-18026: focused map of the SCAF1-containing complex IV from SC respirasome, murine livers  EMDB-18027: global refinement of SC respirasome, murine liver  EMDB-19085: global map of murine liver closed complex I  EMDB-19086: focused map of murine liver complex I peripheral arm in the closed conformation  EMDB-19087: focused map of murine liver complex I membrane arm in the closed conformation  EMDB-19088: global refinement of murine liver complex I in the open conformation  EMDB-19089: focused map of the peripheral arm of complex I from murine liver in the open conformation  EMDB-19090: focused map of the membrane arm of complex I from murine liver in the open conformation  EMDB-19091: global refinement of murine brain complex I in the closed conformation  EMDB-19092: focused map of the peripheral arm of complex I from murine brain in the closed conformation  EMDB-19093: focused map of the membrane arm of murine brain complex I in the closed conformation  EMDB-19105: global refinement of complex I from murine brain in the open conformation  EMDB-19106: focused map of the peripheral arm of murine brain complex I in the open conformation  EMDB-19107: focused map of the membrane arm of murine brain complex I in the open conformation EMDB-19145, PDB-8rgp: EMDB-19146, PDB-8rgq: EMDB-19147, PDB-8rgr: EMDB-19148, PDB-8rgt: |
| Chemicals |  ChemComp-3PE:  ChemComp-CDL:  ChemComp-HEM:  ChemComp-HEC:  ChemComp-FES:  ChemComp-PC1:  ChemComp-CU:  ChemComp-NA:  ChemComp-HEA:  ChemComp-MG:  ChemComp-CUA:  ChemComp-ZN:  ChemComp-TGL:  ChemComp-SF4:  ChemComp-FMN:  ChemComp-K:  ChemComp-NDP:  ChemComp-ZMP:  ChemComp-DGT:  ChemComp-UQ: |
| Source |
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 Keywords |  MEMBRANE PROTEIN / Respiratory chain super complex / mammalian mitochondria / ELECTRON TRANSPORT / respiratory chain complex |
