The Yeast Saccharomyces cerevisiae Contains Two Glutaredoxin Genes That Are Required for Protection against Reactive Oxygen Species

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作者：

S Luikenhuis，G Perrone，IW Dawes，CM Grant

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摘要：

Glutaredoxins are small heat-stable proteins that act as glutathione-dependent disulfide oxidoreductases. Two genes, designatedand , which share 40–52% identity and 61–76% similarity with glutaredoxins from bacterial and mammalian species, were identified in the yeast . Strains deleted for both andwere viable but lacked heat-stable oxidoreductase activity using β-hydroxyethylene disulfide as a substrate. Surprisingly, despite the high degree of homology between Grx1 and Grx2 (64% identity), the mutant was unaffected in oxidoreductase activity, whereas the mutant displayed only 20% of the wild-type activity, indicating that Grx2 accounted for the majority of this activity in vivo. Expression analysis indicated that this difference in activity did not arise as a result of differential expression of and. In addition, a mutant was sensitive to oxidative stress induced by the superoxide anion, whereas a strain that lacked was sensitive to hydrogen peroxide. Sensitivity to oxidative stress was not attributable to altered glutathione metabolism or cellular redox state, which did not vary between these strains. The expression of both genes was similarly elevated under various stress conditions, including oxidative, osmotic, heat, and stationary phase growth. Thus, Grx1 and Grx2 function differently in the cell, and we suggest that glutaredoxins may act as one of the primary defenses against mixed disulfides formed following oxidative damage to proteins.

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关键词：

Humans Saccharomyces cerevisiae Reactive Oxygen Species Oxidoreductases Protein Disulfide Reductase (Glutathione Glutathione Proteins Oxidation-Reduction Oxidative Stress Genes, Fungal