The Yap1p-dependent induction of glutathione synthesis in heat shock response of Saccharomyces cerevisiae.

Glutathione is synthesized in two sequential reactions catalyzed by gamma-glutamylcysteine synthetase (GSH1 gene product) and glutathione synthetase (GSH2 gene product). The expression of GSH1 in Saccharomyces cerevisiae has been known to be up-regulated by Yap1p, a critical transcription factor for the oxidative stress response in yeast. The present study demonstrates that GSH2 expression is also regulated by Yap1p under oxidative stress-induced conditions. In addition to oxidative stress, expression of GSH1 and GSH2 was induced by heat shock stress in a Yap1p-dependent manner with subsequent increases in intracellular glutathione content. Oxygen respiration rate increased when cells were exposed to higher temperatures, and as a result, intracellular oxidation levels were increased. The heat shock-induced expression of GSH1 and GSH2 did not occur under anaerobic conditions. Furthermore, even under aerobic conditions, the heat shock response of these genes was not observed when cells were pretreated with KCN to block oxygen respiration. We speculate that heat shock stress enhances oxygen respiration, which in turn results in an increase in the generation of reactive oxygen species in mitochondria. This signal may be mediated by Yap1p, resulting in the elevation of intracellular glutathione levels.