Cth2 Protein Mediates Early Adaptation of Yeast Cells to Oxidative Stress Conditions

PLoS One. 2016 Jan 29;11(1):e0148204. doi: 10.1371/journal.pone.0148204. eCollection 2016.

Abstract

Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution) upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon). In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Δcth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from α factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics*
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal*
  • Hydrogen Peroxide / pharmacology
  • Ion Transport / drug effects
  • Iron / metabolism*
  • Mating Factor
  • Oxidation-Reduction
  • Oxidative Stress
  • Peptides / genetics
  • Peptides / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Regulon / drug effects
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction
  • Time Factors
  • Tristetraprolin / genetics*
  • Tristetraprolin / metabolism

Substances

  • Peptides
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • TIS11 protein, S cerevisiae
  • Tristetraprolin
  • Mating Factor
  • Hydrogen Peroxide
  • Iron

Grants and funding

This study was supported by grant BFU2010-17656 from Spanish Ministerio de Economía y Competitividad (www.mineco.gob.es). JP was the recipient of a predoctoral grant from Ministerio de Economía y Competitividad. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.