title: The mitochondrial quality control protein Yme1 is necessary to prevent defective mitophagy in a yeast model of Barth syndrome.
abstract: The Saccharomyces cerevisiae TAZ1 gene is an orthologue of human TAZ; both encode the protein tafazzin. Tafazzin is a transacylase that transfers acyl chains with unsaturated fatty acids from phospholipids to monolysocardiolipin to generate cardiolipin with unsaturated fatty acids. Mutations in human TAZ cause Barth syndrome, a fatal childhood cardiomyopathy biochemically characterized by reduced cardiolipin mass and increased monolysocardiolipin levels. To uncover cellular processes that require tafazzin to maintain cell health, we performed a synthetic genetic array screen using taz1Δ yeast cells to identify genes whose deletion aggravated its fitness. The synthetic genetic array screen uncovered several mitochondrial cellular processes that require tafazzin. Focusing on the i-AAA protease Yme1, a mitochondrial quality control protein that degrades misfolded proteins, we determined that in cells lacking both Yme1 and Taz1 function, there were substantive mitochondrial ultrastructural defects, ineffective superoxide scavenging, and a severe defect in mitophagy. We identify an important role for the mitochondrial protease Yme1 in the ability of cells that lack tafazzin function to maintain mitochondrial structural integrity and mitochondrial quality control and to undergo mitophagy.
authors: From the Departments of Biochemistry and Molecular Biology and.
authors: Gerard J
authors: GJ
authors: Gaspard
authors: From the Departments of Biochemistry and Molecular Biology and Pharmacology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada Christopher.mcmaster@dal.ca.
authors: Christopher R
authors: CR
authors: McMaster
mesh_terms: D049069:ATP-Dependent Proteases / Q000502:physiology*; D000217:Acyltransferases / Q000235:genetics; D056889:Barth Syndrome / Q000235:genetics / Q000503:physiopathology*; D001483:Base Sequence; D017931:DNA Primers; D024101:Mitochondrial Proteins / Q000502:physiology*; D063306:Mitophagy / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D063347:Native Polyacrylamide Gel Electrophoresis; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D000217:Acyltransferases; C481660:Taz1 protein, S cerevisiae; D049069:ATP-Dependent Proteases; C082702:YME1 protein, S cerevisiae
keywords: Cardiolipin; Cardiomyopathy; Inborn Error of Metabolism; Lipid; Lipid Metabolism; Membrane Lipid; Mitophagy; Phospholipid Metabolism; Saccharomyces cerevisiae; Yeast Genetics