Role of glutathione in heat-shock-induced cell death of Saccharomyces cerevisiae

Previously we reported that expression of GSH1 (γ-glutamylcysteine synthetase) and GSH2 (glutathione synthetase) of the yeast Saccharomyces cere isiae was increased by heat-shock stress in a Yap1p-dependent fashion and consequently intracellular glutathione content was increased [Sugiyama, Izawa and Inoue (2000) J. Biol.Chem.275, 15535-15540].In the present study, we discuss the physiological role of glutathione in the heat-shock stress response in this yeast.Both gsh1 and gsh2 mutants could acquire thermotolerance by mild heat-shock stress and induction of Hsp104p in both mutants was normal ; however, mutant cells died faster by heat shock than their parental wildtype strain.After pretreatment at a sublethal temperature, the number of respiration-deficient mutants increased in a gsh1 mutant strain in the early stages of exposure to a lethal temperature, although this increase was partially suppressed by the addition of glutathione.These results lead us to suspect that Abbreviations used : HSP, heat-shock protein; SOD,