title: The role of the yeast ATP-binding cassette Ycf1p in glutathione and cadmium ion homeostasis during respiratory metabolism.
abstract: Cadmium (Cd2+) is a toxic environmental contaminant for biological systems, which can form complexes with reduced glutathione (GSH), and thus alter the intracellular redox state. In Saccharomyces (S.) cerevisiae, bis(glutathionato)cadmium (Cd-[GS]2) complexes can be removed from the cytosol and transported into the vacuole by a glutathione-conjugated pump, Ycf1p. In this study, we investigated the role of Ycf1p in Cd2+ detoxification during respiratory metabolism of S. cerevisiae, and the correlation of Ycf1p with GSH intracellular homeostasis. The results showed that in respiratory condition the mutant ycf1Delta is more tolerant to Cd2+ and to the oxidants t-BOOH and H2O2 than wild-type strain. This tolerance is probably related to the high content of GSH present in ycf1Delta mutant. The expression of YCF1 promoter in the wild-type strain is naturally down-regulated after the transition from fermentative to respiratory metabolism (diauxic shift), and its induction in response to Cd2+ is dependent on GSH availability. Our data suggest that Ycf1p is involved in the maintenance of intracellular GSH homeostasis and it can interfere with the oxidative tolerance of yeast. Moreover, the detoxification of Cd2+ is dependent on GSH availability and on cellular metabolic status.
authors.affiliation: CBiot/Instituto de Biologia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9500, Prédio 43421, Sala 113, Porto Alegre, RS 91507-970, Brazil.
authors.forename: Albanin Aparecida
authors.initials: AA
authors.lastname: Mielniczki-Pereira
authors.forename: Ana Zilles
authors.initials: AZ
authors.lastname: Schuch
authors.forename: Diego
authors.initials: D
authors.lastname: Bonatto
authors.forename: Cátia Ferreira
authors.initials: CF
authors.lastname: Cavalcante
authors.forename: Delmo Santiago
authors.initials: DS
authors.lastname: Vaitsman
authors.forename: Cristiano Jorge
authors.initials: CJ
authors.lastname: Riger
authors.forename: Elis Cristina Araujo
authors.initials: EC
authors.lastname: Eleutherio
authors.forename: João Antonio Pêgas
authors.initials: JA
authors.lastname: Henriques
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D019256:Cadmium Chloride / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007477:Ions; D016877:Oxidants / Q000633:toxicity; D010101:Oxygen Consumption / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D018528:ATP-Binding Cassette Transporters; D007477:Ions; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; C089179:YCF1 protein, S cerevisiae; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D005978:Glutathione; D019256:Cadmium Chloride