title: SLC25 Family Member Genetic Interactions Identify a Role forHEM25in Yeast Electron Transport Chain Stability.
abstract: The SLC25 family member SLC25A38 (Hem25 in yeast) was recently identified as a mitochondrial glycine transporter that provides substrate to initiate heme/hemoglobin synthesis. Mutations in the humanSLC25A38gene cause congenital sideroblastic anemia. The full extent to which SLC25 family members coregulate heme synthesis with other mitochondrial functions is not clear. In this study, we surveyed 29 nonessential SLC25 family members inSaccharomyces cerevisiaefor their ability to support growth in the presence and absence ofHEM25Six SLC25 family members were identified that were required for growth or for heme synthesis in cells lacking Hem25 function. Importantly, we determined that loss of function of the SLC25 family member Flx1, which imports FAD into mitochondria, together with loss of function of Hem25, resulted in inability to grow on media that required yeast cells to supply energy using mitochondrial respiration. We report that specific components of complexes of the electron transport chain are decreased in the absence of Flx1 and Hem25 function. In addition, we show that mitochondria fromflx1Δhem25Δ cells contain uncharacterized Cox2-containing high molecular weight aggregates. The functions of Flx1 and Hem25 provide a facile explanation for the decrease in heme level, and in specific electron transport chain complex components.
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3N 0A1, Canada.
authors.forename: J Noelia
authors.initials: JN
authors.lastname: Dufay
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia B3N 0A1, Canada.
authors.forename: J Pedro
authors.initials: JP
authors.lastname: Fernández-Murray
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia B3N 0A1, Canada christopher.mcmaster@dal.ca.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McMaster
mesh_terms: D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D004579:Electron Transport; D004843:Epistasis, Genetic; D017353:Gene Deletion; D056726:Genetic Association Studies; D005998:Glycine / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D010641:Phenotype; D055550:Protein Stability; D012641:Selection, Genetic; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D006418:Heme; D005998:Glycine
keywords: SLC25 protein family; electron transport chain; glycine import; heme; mitochondria