The role of the yeast ATP-binding cassette Ycf1p in glutathione and cadmium ion homeostasis during respiratory metabolism

Cadmium (Cd 2+) is a toxic environmental contaminant for biological systems, which can form complexes with reduced glutathione (GSH), and thus alter the intracellular redox state. In Saccharomyces ( S.) cerevisiae, bis(glutathionato)cadmium (Cd–[GS] 2) complexes can be removed from the cytosol and transported into the vacuole by a glutathione-conjugated pump, Ycf1p. In this study, we investigated the role of Ycf1p in Cd 2+ detoxification during respiratory metabolism of S. cerevisiae, and the correlation of Ycf1p with GSH intracellular homeostasis. The results showed that in respiratory condition the mutant ycf1Δ is more tolerant to Cd 2+ and to the oxidants t-BOOH and H 2O 2 than wild-type strain. This tolerance is probably related to the high content of GSH present in ycf1Δ mutant. The expression of YCF1 promoter in the wild-type strain is naturally down-regulated after the transition from fermentative to respiratory metabolism (diauxic shift), and its induction in response to Cd 2+ is dependent on GSH availability. Our data suggest that Ycf1p is involved in the maintenance of intracellular GSH homeostasis and it can interfere with the oxidative tolerance of yeast. Moreover, the detoxification of Cd 2+ is dependent on GSH availability and on cellular metabolic status.