8.A.224.  The Splicing factor, Arginine/Serine-rich 19 (SCAF1) Family 

The enzymes of the mitochondrial electron transport chain associate into supercomplexes. Supercomplexes CIII₂CIV_1-2, CICIII₂ and CICIII₂CIV (respirasome) exist in mammals, but in contrast to CICIII₂ and the respirasome, CIII₂CIV requires a specific assembly factor (SCAF1) to be formed. Dr. Irene Vercellino solved the structures of mammalian (mouse and ovine) CIII₂CIV and its assembly intermediates in different conformations (Vercellino and Sazanov 2021). These allowed description of the assembly of CIII₂CIV from the CIII₂ precursor to the final CIII₂CIV conformation, driven by the insertion of the N terminus of SCAF1 deep into CIII₂, while its C terminus is integrated into CIV. The structures confirmed that SCAF1 is exclusively required for the assembly of CIII₂CIV and has no role in the assembly of the respirasome. Further, 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. Biochemical analyses showed that CIII₂ and CIV gain catalytic advantage when assembled into the supercomplex, suggesting a role for CIII₂CIV in fine tuning the efficiency of electron transfer in the electron transport chain (Vercellino and Sazanov 2021).