Genetic Analysis of Glutathione Peroxidase in Oxidative Stress Response of Saccharomyces cerevisiae *

Three glutathione peroxidase homologs (YKL026C, YBR244W, andYIR037W/HYR1) were found in theSaccharomyces Genome Database. We named themGPX1, GPX2, and GPX3, respectively, and we investigated the function of each gene product. Thegpx3Δ mutant was hypersensitive to peroxides, whereas null mutants of the GPX1 and GPX2 did not show any obvious phenotypes. Glutathione peroxidase activity decreased approximately 57 and 93% in the gpx3Δ andgpx1Δ/gpx2Δ/gpx3Δ mutants, respectively, compared with that of wild type. Expression of theGPX3 gene was not induced by any stresses tested, whereas that of the GPX1 gene was induced by glucose starvation. The GPX2 gene expression was induced by oxidative stress, which was dependent upon the Yap1p. The TSA1(thiol-specific antioxidant) gene encodes thioredoxin peroxidase that can reduce peroxides by using thioredoxin as a reducing power. Disruption of the TSA1 gene enhanced the basal expression level of the Yap1p target genes such as GSH1,GLR1, and GPX2 and that resulted in increases of total glutathione level and activities of glutathione reductase and glutathione peroxidase. However, expression of the TSA1gene did not increase in thegpx1Δ/gpx2Δ/gpx3Δ mutant. Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Δ mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase.

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