title: CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter.
abstract: Mitochondrial calcium is an important modulator of cellular metabolism. CCDC90A was reported to be a regulator of the mitochondrial calcium uniporter (MCU) complex, a selective channel that controls mitochondrial calcium uptake, and hence was renamed MCUR1. Here we show that suppression of CCDC90A in human fibroblasts produces a specific cytochrome c oxidase (COX) assembly defect, resulting in decreased mitochondrial membrane potential and reduced mitochondrial calcium uptake capacity. Fibroblasts from patients with COX assembly defects due to mutations in TACO1 or COX10 also showed reduced mitochondrial membrane potential and impaired calcium uptake capacity, both of which were rescued by expression of the respective wild-type cDNAs. Deletion of fmp32, a homolog of CCDC90A in Saccharomyces cerevisiae, an organism that lacks an MCU, also produces a COX deficiency, demonstrating that the function of CCDC90A is evolutionarily conserved. We conclude that CCDC90A plays a role in COX assembly and does not directly regulate MCU.
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Paupe
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada; Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Prudent
authors.affiliation: University of Paris-Sud, CNRS, UMR 8621, Institute of Genetics and Microbiology, Orsay, France.
authors.forename: Emmanuel P
authors.initials: EP
authors.lastname: Dassa
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Olga Zurita
authors.initials: OZ
authors.lastname: Rendon
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 2B4, Canada. Electronic address: eric@ericpc.mni.mcgill.ca.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Shoubridge
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D030401:Cytochrome-c Oxidase Deficiency / Q000378:metabolism / Q000473:pathology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D045222:Electron Transport Chain Complex Proteins; C000601188:MCUR1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins; C034703:mitochondrial calcium uniporter; C490115:COX10 protein, human; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases; D002118:Calcium