title: The yeast oligopeptide transporter Opt2 is localized to peroxisomes and affects glutathione redox homeostasis.
abstract: Glutathione, the most abundant small-molecule thiol in eukaryotic cells, is synthesized de novo solely in the cytosol and must subsequently be transported to other cellular compartments. The mechanisms of glutathione transport into and out of organelles remain largely unclear. We show that budding yeast Opt2, a close homolog of the plasma membrane glutathione transporter Opt1, localizes to peroxisomes. We demonstrate that deletion of OPT2 leads to major defects in maintaining peroxisomal, mitochondrial, and cytosolic glutathione redox homeostasis. Furthermore, ∆opt2 strains display synthetic lethality with deletions of genes central to iron homeostasis that require mitochondrial glutathione redox homeostasis. Our results shed new light on the importance of peroxisomes in cellular glutathione homeostasis.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Elbaz-Alon
authors.forename: Bruce
authors.initials: B
authors.lastname: Morgan
authors.forename: Anne
authors.initials: A
authors.lastname: Clancy
authors.forename: Theresa N E
authors.initials: TN
authors.lastname: Amoako
authors.forename: Einat
authors.initials: E
authors.lastname: Zalckvar
authors.forename: Tobias P
authors.initials: TP
authors.lastname: Dick
authors.forename: Blanche
authors.initials: B
authors.lastname: Schwappach
authors.forename: Maya
authors.initials: M
authors.lastname: Schuldiner
mesh_terms: D017353:Gene Deletion; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis; D026901:Membrane Transport Proteins / Q000032:analysis* / Q000235:genetics; D009842:Oligopeptides / Q000378:metabolism*; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis* / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; C000598906:OPT2 protein, S cerevisiae; D009842:Oligopeptides; D029701:Saccharomyces cerevisiae Proteins; D005978:Glutathione
keywords: GSH; GSSG; Grx1-roGFP2; glutathione homeostasis; peroxisome