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Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP‐binding cassette transporter Ycf1p
Author(s) -
Lazard Myriam,
HaDuong NguyetThanh,
Mounié Stéphanie,
Perrin Romary,
Plateau Pierre,
Blanquet Sylvain
Publication year - 2011
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08318.x
Subject(s) - glutathione , saccharomyces cerevisiae , vacuole , transporter , atp binding cassette transporter , biochemistry , toxicity , plasmid , chemistry , biology , enzyme , yeast , gene , cytoplasm , organic chemistry
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 Microbiol 36 , 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.