CIA2 deficiency results in impaired oxidative stress response and enhanced intracellular basal UPR activity in Saccharomyces cerevisiae

FEMS Microbiol Lett. 2015 Mar;362(6):fnv013. doi: 10.1093/femsle/fnv013. Epub 2015 Feb 8.

Abstract

Yeast Cia2p is a component of the cytosolic Fe/S protein assembly (CIA) machinery. Initial studies of the CIA machinery were performed in yeast, but the precise role of Cia2p in this eukaryote is still unknown. We report that CIA2 deficiency results in impaired oxidative stress response, as evidenced by increased sensitivity to the oxidant cumene hydroperoxide (CHP), impaired activities of superoxide dismutases and aconitase and decreased replicative lifespan in the mutants. Moreover, intracellular reactive oxygen species levels were significantly increased in CIA2-deficient cells after treatment with CHP. We also show that CIA2-deficient cells display an increased resistance to tunicamycin-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulated splicing of the mRNA of HAC1, which encodes a functional transcription factor that regulates the transcription of unfolded protein response (UPR) target genes, suggesting enhanced intracellular UPR activity. Furthermore, the transcription of several canonical UPR target genes is strongly induced in CIA2-deficient cells as compared with wild-type controls. Taken together, these results suggest the involvement of Cia2p in oxidative and ER stress responses in yeast.

Keywords: CIA2; UPR; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Benzene Derivatives / pharmacology
  • Cytoplasm / genetics
  • Cytoplasm / physiology
  • Endoplasmic Reticulum Stress*
  • Mutation
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Signal Transduction
  • Transcription Factors
  • Tunicamycin / pharmacology
  • Unfolded Protein Response* / genetics
  • Up-Regulation

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Benzene Derivatives
  • HAC1 protein, S cerevisiae
  • Reactive Oxygen Species
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • YHR122W protein, S cerevisiae
  • Tunicamycin
  • cumene hydroperoxide