The oxidative stress response in yeast cells involves changes in the stability of Aft1 regulon mRNAs

Mol Microbiol. 2011 Jul;81(1):232-48. doi: 10.1111/j.1365-2958.2011.07689.x. Epub 2011 May 25.

Abstract

Saccharomyces cerevisiae can import iron through a high-affinity system consisting of the Ftr1/Fet3-mediated reductive pathway and the siderophore-mediated non-reductive one. Expression of components of the high-affinity system is controlled by the Aft1 transcriptional factor. In this study we show that, upon oxidative stress, Aft1 is transitorily internalized into the nucleus, followed by transcription activation of components of its regulon. In these conditions, the mRNA levels of the genes of the non-reductive pathway become increased, while those of FTR1 and FET3 remain low because of destabilization of the mRNAs. Consequently, the respective protein levels also remain low. Such mRNA destabilization is mediated by the general 5'-3' mRNA decay pathway and is independent of the RNA binding protein Cth2. Yeast cells are hypersensitive to peroxides in growth conditions where only the high-affinity reductive pathway is functional for iron assimilation. On the contrary, peroxide does not affect growth when iron uptake occurs exclusively through the non-reductive pathway. This reinforces the idea that upon oxidative stress S. cerevisiae cells redirect iron assimilation through the non-reductive pathway to minimize oxidative damage by the ferrous ions, which are formed during iron import through the Ftr1/Fet3 complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ceruloplasmin / metabolism
  • Gene Expression Regulation, Fungal*
  • Hydrogen Peroxide / toxicity
  • Iron / metabolism
  • Membrane Transport Proteins / metabolism
  • Oxidants / toxicity
  • Oxidative Stress*
  • RNA Stability*
  • Regulon*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / metabolism*

Substances

  • AFT1 protein, S cerevisiae
  • FTR1 protein, S cerevisiae
  • Membrane Transport Proteins
  • Oxidants
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Hydrogen Peroxide
  • Iron
  • Ceruloplasmin
  • FET3 protein, S cerevisiae