A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae : YCF1-catalyzed transport of bis(glutathionato)cadmium

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Abstract
The yeast cadmium factor ( YCF1 ) gene encodes an MgATP-energized glutathione S -conjugate transporter responsible for the vacuolar sequestration of organic compounds after their S -conjugation with glutathione. However, while YCF1 was originally isolated according to its ability to confer resistance to cadmium salts, neither its mode of interaction with Cd 2+ nor the relationship between this process and organic glutathione-conjugate transport are known. Here we show through direct comparisons between vacuolar membrane vesicles purified from Saccharomyces cerevisiae strain DTY167, harboring a deletion of the YCF1 gene, and the isogenic wild-type strain DTY165 that YCF1 mediates the MgATP-energized vacuolar accumulation of Cd·glutathione complexes. The substrate requirements, kinetics and Cd 2+ /glutathione stoichiometry of cadmium uptake and the molecular weight of the transport-active complex demonstrate that YCF1 selectively catalyzes the transport of bis(glutathionato)cadmium (Cd·GS 2 ). On the basis of these results—the Cd 2+ hypersensitivity of DTY167, versus DTY165, cells, the inducibility of YCF1-mediated transport, and the rapidity and spontaneity of Cd·GS 2 formation—this new pathway is concluded to contribute substantially to Cd 2+ detoxification.