CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter.

TitleCCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter.
Publication TypeJournal Article
Year of Publication2015
AuthorsPaupe, V, Prudent, J, Dassa, EP, Rendon, OZurita, Shoubridge, EA
JournalCell Metab
Date Published2015 Jan 6
KeywordsAlkyl and Aryl Transferases, Calcium, Calcium Channels, Cells, Cultured, Cytochrome-c Oxidase Deficiency, Electron Transport Chain Complex Proteins, Electron Transport Complex IV, Fibroblasts, Humans, Membrane Potential, Mitochondrial, Membrane Proteins, Mitochondria, Mitochondrial Proteins, Mutation, RNA Interference, RNA, Small Interfering, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins

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.

Alternate JournalCell Metab.
Citation Key10.1016/j.cmet.2014.12.004
PubMed ID25565209
Grant List / / Canadian Institutes of Health Research / Canada