title: C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1 complex assembly and supercomplex stabilization.
abstract: Mammalian mitochondria may contain up to 1,500 different proteins, and many of them have neither been confidently identified nor characterized. In this study, we demonstrated that C11orf83, which was lacking experimental characterization, is a mitochondrial inner membrane protein facing the intermembrane space. This protein is specifically associated with the bc1 complex of the electron transport chain and involved in the early stages of its assembly by stabilizing the bc1 core complex. C11orf83 displays some overlapping functions with Cbp4p, a yeast bc1 complex assembly factor. Therefore, we suggest that C11orf83, now called UQCC3, is the functional human equivalent of Cbp4p. In addition, C11orf83 depletion in HeLa cells caused abnormal crista morphology, higher sensitivity to apoptosis, a decreased ATP level due to impaired respiration and subtle, but significant, changes in cardiolipin composition. We showed that C11orf83 binds to cardiolipin by its α-helices 2 and 3 and is involved in the stabilization of bc1 complex-containing supercomplexes, especially the III2/IV supercomplex. We also demonstrated that the OMA1 metalloprotease cleaves C11orf83 in response to mitochondrial depolarization, suggesting a role in the selection of cells with damaged mitochondria for their subsequent elimination by apoptosis, as previously described for OPA1.
authors.affiliation: Department of Human Protein Sciences, University of Geneva, Geneva, Switzerland marjorie.desmurs@unige.ch lydie.lane@isb-sib.ch.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Desmurs
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Foti
authors.affiliation: Department of Cell Biology, University of Geneva, Geneva, Switzerland.
authors.forename: Etienne
authors.initials: E
authors.lastname: Raemy
authors.affiliation: Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frédéric Maxime
authors.initials: FM
authors.lastname: Vaz
authors.affiliation: Department of Cell Biology, University of Geneva, Geneva, Switzerland.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Martinou
authors.affiliation: Department of Human Protein Sciences, University of Geneva, Geneva, Switzerland CALIPHO Group, SIB Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors.forename: Amos
authors.initials: A
authors.lastname: Bairoch
authors.affiliation: Department of Human Protein Sciences, University of Geneva, Geneva, Switzerland CALIPHO Group, SIB Swiss Institute of Bioinformatics, Geneva, Switzerland marjorie.desmurs@unige.ch lydie.lane@isb-sib.ch.
authors.forename: Lydie
authors.initials: L
authors.lastname: Lane
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002308:Cardiolipins / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D014450:Electron Transport Complex III / Q000378:metabolism*; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D014981:Xenopus
chemical_list: D002308:Cardiolipins; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; C000597855:UQCC3 protein, human; D008666:Metalloendopeptidases; C477817:molecule metalloprotease-related protein-1, human; D014450:Electron Transport Complex III