title: Identification of a protein mediating respiratory supercomplex stability.
abstract: The complexes of the electron transport chain associate into large macromolecular assemblies, which are believed to facilitate efficient electron flow. We have identified a conserved mitochondrial protein, named respiratory supercomplex factor 1 (Rcf1-Yml030w), that is required for the normal assembly of respiratory supercomplexes. We demonstrate that Rcf1 stably and independently associates with both Complex III and Complex IV of the electron transport chain. Deletion of the RCF1 gene caused impaired respiration, probably as a result of destabilization of respiratory supercomplexes. Consistent with the hypothetical function of these respiratory assemblies, loss of RCF1 caused elevated mitochondrial oxidative stress and damage. Finally, we show that knockdown of HIG2A, a mammalian homolog of RCF1, causes impaired supercomplex formation. We suggest that Rcf1 is a member of an evolutionarily conserved protein family that acts to promote respiratory supercomplex assembly and activity.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Yu-Chan
authors.initials: YC
authors.lastname: Chen
authors.forename: Eric B
authors.initials: EB
authors.lastname: Taylor
authors.forename: Noah
authors.initials: N
authors.lastname: Dephoure
authors.forename: Jin-Mi
authors.initials: JM
authors.lastname: Heo
authors.forename: Aline
authors.initials: A
authors.lastname: Tonhato
authors.forename: Ioanna
authors.initials: I
authors.lastname: Papandreou
authors.forename: Nandita
authors.initials: N
authors.lastname: Nath
authors.forename: Nicolas C
authors.initials: NC
authors.lastname: Denko
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Jared
authors.initials: J
authors.lastname: Rutter
mesh_terms: D000818:Animals; D002460:Cell Line; D019069:Cell Respiration / Q000235:genetics / Q000502:physiology*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I