title: Glutathione serves an extracellular defence function to decrease arsenite accumulation and toxicity in yeast.
abstract: Arsenic is an environmental toxin and a worldwide health hazard. Since this metalloid is ubiquitous in nature, virtually all living organisms require systems for detoxification and tolerance acquisition. Here, we show that during chronic exposure to arsenite [As(III)], Saccharomyces cerevisiae (budding yeast) exports and accumulates the low-molecular-weight thiol molecule glutathione (GSH) outside of cells. Extracellular accumulation of the arsenite triglutathione complex As(GS)₃ was also detected and direct transport assays demonstrate that As(GS)₃ does not readily enter cells. Yeast cells with increased extracellular GSH levels accumulate less arsenic and display improved growth when challenged with As(III). Conversely, cells defective in export and extracellular accumulation of GSH are As(III) sensitive. Taken together, our data are consistent with a novel detoxification mechanism in which GSH is exported to protect yeast cells from arsenite toxicity by preventing its uptake.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, S-40530 Gothenburg, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Thorsen
authors.forename: Therese
authors.initials: T
authors.lastname: Jacobson
authors.forename: Riet
authors.initials: R
authors.lastname: Vooijs
authors.forename: Clara
authors.initials: C
authors.lastname: Navarrete
authors.forename: Tijs
authors.initials: T
authors.lastname: Bliek
authors.forename: Henk
authors.initials: H
authors.lastname: Schat
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Tamás
mesh_terms: D000935:Antifungal Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018053:Arsenites / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D008658:Inactivation, Metabolic; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D018053:Arsenites; D005978:Glutathione; C015001:arsenite