title: Gex1 is a yeast glutathione exchanger that interferes with pH and redox homeostasis.
abstract: In the yeast Saccharomyces cerevisiae, glutathione plays a major role in heavy metal detoxification and protection of cells against oxidative stress. We show that Gex1 is a new glutathione exchanger. Gex1 and its paralogue Gex2 belong to the major facilitator superfamily of transporters and display similarities to the Aft1-regulon family of siderophore transporters. Gex1 was found mostly at the vacuolar membrane and, to a lesser extent, at the plasma membrane. Gex1 expression was induced under conditions of iron depletion and was principally dependent on the iron-responsive transcription factor Aft2. However, a gex1Δ gex2Δ strain displayed no defect in known siderophore uptake. The deletion mutant accumulated intracellular glutathione, and cells overproducing Gex1 had low intracellular glutathione contents, with glutathione excreted into the extracellular medium. Furthermore, the strain overproducing Gex1 induced acidification of the cytosol, confirming the involvement of Gex1 in proton transport as a probable glutathione/proton antiporter. Finally, the imbalance of pH and glutathione homeostasis in the gex1Δ gex2Δ and Gex1-overproducing strains led to modulations of the cAMP/protein kinase A and protein kinase C1 mitogen-activated protein kinase signaling pathways.
authors.affiliation: Laboratoire Ubiquitine et Trafic Intracellulaire, Institut Jacques Monod, UMR 7592 CNRS-Université Paris-Diderot, France.
authors.forename: Manel
authors.initials: M
authors.lastname: Dhaoui
authors.forename: Françoise
authors.initials: F
authors.lastname: Auchère
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Blaiseau
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lesuisse
authors.forename: Ahmed
authors.initials: A
authors.lastname: Landoulsi
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Camadro
authors.forename: Rosine
authors.initials: R
authors.lastname: Haguenauer-Tsapis
authors.forename: Naïma
authors.initials: N
authors.lastname: Belgareh-Touzé
mesh_terms: D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D020935:MAP Kinase Signaling System; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C090297:AFT1 protein, S cerevisiae; C436328:Aft2 protein, S cerevisiae; D017920:Antiporters; D001425:Bacterial Outer Membrane Proteins; C568434:Gex1 protein, S cerevisiae; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C035902:siderophore receptors; D002104:Cadmium; D000242:Cyclic AMP; D007501:Iron; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005978:Glutathione