The H2O2 Stimulon in Saccharomyces cerevisiae

TLDR

The study provides the first genome‑wide characterization of a H₂O₂‑inducible stimulon in a eukaryote. The authors used comparative two‑dimensional gel electrophoresis of total cell proteins and analyzed the kinetics and dose‑response of the H₂O₂ genomic response. H₂O₂ induces synthesis of 115 proteins and repression of 52, including heat‑shock proteins and ROS‑scavenging enzymes, while slowing protein synthesis, boosting degradation, and rapidly redirecting carbohydrate metabolism toward NADPH regeneration.

Abstract

The changes in gene expression underlying the yeast adaptive stress response to H₂O₂were analyzed by comparative two-dimensional gel electrophoresis of total cell proteins. The synthesis of at least 115 proteins is stimulated by H₂O₂, whereas 52 other proteins are repressed by this treatment. We have identified 71 of the stimulated and 44 of the repressed targets. The kinetics and dose-response parameters of the H₂O₂ genomic response were also analyzed. Identification of these proteins and their mapping into specific cellular processes give a distinct picture of the way in which yeast cells adapt to oxidative stress. As expected, H₂O₂-responsive targets include an important number of heat shock proteins and proteins with reactive oxygen intermediate scavenging activities. Exposure to H₂O₂ also results in a slowdown of protein biosynthetic processes and a stimulation of protein degradation pathways. Finally, the most remarkable result inferred from this study is the resetting of carbohydrate metabolism minutes after the exposure to H₂O₂. Carbohydrate fluxes are redirected to the regeneration of NADPH at the expense of glycolysis. This study represents the first genome-wide characterization of a H₂O₂-inducible stimulon in a eukaryote.