Involvement of Gtr1p in the oxidative stress response in yeast Saccharomyces cerevisiae

Biochem Biophys Res Commun. 2022 Apr 2:598:107-112. doi: 10.1016/j.bbrc.2022.02.016. Epub 2022 Feb 8.

Abstract

Yeast Gtr1p is a GTPase that forms a heterodimer with Gtr2p, another GTPase; it is involved in regulating TORC1 activity in nutrient signaling, including amino acid availability and growth control. Gtr1p is a positive regulator of TORC1, a kinase that regulates various cellular functions (e.g., protein synthesis and autophagy) under specific nutrient and environmental conditions, including oxidative stress. In this study, we examined the roles of Gtr1p in oxidative stress responses. We found that yeast cells expressing guanosine diphosphatase (GDP)-bound Gtr1p (Gtr1-S20Lp) were resistant to hydrogen peroxide (H2O2), whereas guanosine triphosphate (GTP)-bound Gtr1p (Gtr1-Q65Lp) was sensitive to H2O2 compared with the wild type. Consistent with these findings, yeast cells lacking Iml1p, a component of the GTPase-activating protein complex for Gtr1p, exhibited the H2O2-sensitive phenotype. In gtr1S20L cells, autophagy was highly induced under oxidative stress. gtr1Q65L cells showed decreased expression of the SNQ2 gene, which encodes a multidrug transporter involved in resistance to oxidative stress, and the overexpression of SNQ2 rescued the oxidative stress sensitivity of gtr1Q65L cells. These results suggest that Gtr1p is involved in oxidative stress responses through mechanisms that include autophagy and SNQ2 expression.

Keywords: Autophagy; Gtr1p; Oxidative stress; SNQ2; TORC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Autophagy
  • Gene Expression Regulation, Fungal
  • Hydrogen Peroxide / pharmacology
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Gtr1 protein, S cerevisiae
  • SNQ2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Hydrogen Peroxide
  • Monomeric GTP-Binding Proteins