TAILIEUCHUNG - Báo cáo khoa hoc : Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p

TheSaccharomyces 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 YCF1was shown to confer increased resistance, rather than sensitivity | IFEBS Journal Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p Myriam Lazard Nguyet-Thanh Ha-Duong Stephanie Mounie Romary Perrin Pierre Plateau and Sylvain Blanquet Ecole polytechnique Laboratoire de Biochimie CNRS Palaiseau France Keywords ABC-protein GSH GSSG ratio selenium YCF1 yeast secretory vesicles Correspondence M. Lazard Laboratoire de Biochimie Ecole polytechnique 91128 Palaiseau Cedex France Fax 33 1 69 33 49 09 Tel 33 1 69 33 48 85 E-mail Present address Laboratoire ITODYS Interfaces Traite-ments Organisation et Dynamique des Systemes Universite Paris Diderot France Received 22 April 2011 revised 13 July 2011 accepted 12 August 2011 The Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycflp 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 Ycflp 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 Ycflp impairs the glutathione oxidized glutathione ratio of cells subjected to a selenite stress. Possible mechanisms by which Ycflp-medi-ated vacuolar uptake of selenodiglutathione and oxidized glutathione enhances selenite toxicity are discussed. doi Introduction One important pathway in cellular detoxification relies on the .

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