A NEW PATHWAY FOR VACUOLAR CADMIUM SEQUESTRATION IN SACCHAROMYCES-CEREVISIAE - YCF1-CATALYZED TRANSPORT OF BIS(GLUTATHIONATO)CADMIUM

The yeast cadmium factor (YCF1) gene encodes an MgATP-energized glutat hione S-conjugate transporter responsible for the vacuolar sequestrati on of organic compounds after their S-conjugation with glutathione. Ho wever, while YCF1 was originally isolated according to its ability to confer resistance to cadmium salts, neither its mode of interaction wi th Cd2+ nor the relationship between this process and organic glutathi one-conjugate transport are known. Here we show through direct compari sons between vacuolar membrane vesicles purified from Saccharomyces ce revisiae strain DTY167, harboring a deletion of the YCF1 gene, and the isogenic wild-type strain DTY165 that YCF1 mediates the MgATP-energiz ed vacuolar accumulation of Cd . glutathione complexes, The substrate requirements, kinetics and Cd2+/ glutathione stoichiometry of cadmium uptake and the molecular weight of the transport-active complex demons trate that YCF1 selectively catalyzes the transport of bis(glutathiona to)cadmium (Cd . GS(2)). On the basis of these results-the Cd2+ hypers ensitivity of DTY167, versus DTY165, cells, the inducibility of YCF1-m ediated transport, and the rapidity and spontaneity of Cd . GS(2) form ation-this new pathway is concluded to contribute substantially to Cd2 + detoxification.