title: Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p.
abstract: The Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p is involved in heavy metal detoxification by mediating the ATP-dependent transport of glutathione-metal conjugates to the vacuole. In the case of selenite toxicity, deletion of YCF1 was shown to confer increased resistance, rather than sensitivity, to selenite exposure [Pinson B, Sagot I & Daignan-Fornier B (2000) Mol Microbiol36, 679-687]. Here, we show that when Ycf1p is expressed from a multicopy plasmid, the toxicity of selenite is exacerbated. Using secretory vesicles isolated from a sec6-4 mutant transformed either with the plasmid harbouring YCF1 or the control plasmid, we establish that the glutathione-conjugate selenodigluthatione is a high-affinity substrate of this ATP-binding cassette transporter and that oxidized glutathione is also efficiently transported. Finally, we show that the presence of Ycf1p impairs the glutathione/oxidized glutathione ratio of cells subjected to a selenite stress. Possible mechanisms by which Ycf1p-mediated vacuolar uptake of selenodiglutathione and oxidized glutathione enhances selenite toxicity are discussed.
authors: Ecole polytechnique, Laboratoire de Biochimie, CNRS, Palaiseau, France. myriam.lazard@polytechnique.edu
authors: Myriam
authors: M
authors: Lazard
authors: Nguyet-Thanh
authors: NT
authors: Ha-Duong
authors: Stéphanie
authors: S
authors: Mounié
authors: Romary
authors: R
authors: Perrin
authors: Pierre
authors: P
authors: Plateau
authors: Sylvain
authors: S
authors: Blanquet
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D016566:Organoselenium Compounds / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D016566:Organoselenium Compounds; D029701:Saccharomyces cerevisiae Proteins; C089179:YCF1 protein, S cerevisiae; C017710:selenodiglutathione; D000255:Adenosine Triphosphate; D005978:Glutathione