The budding yeast orthologue of Parkinson's disease-associated DJ-1 is a multi-stress response protein protecting cells against toxic glycolytic products

Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):39-50. doi: 10.1016/j.bbamcr.2016.10.016. Epub 2016 Oct 27.

Abstract

Saccharomyces cerevisiae Hsp31p is a DJ-1/ThiJ/PfpI family protein that was previously shown to be important for survival in the stationary phase of growth and under oxidative stress. Recently, it was identified as a chaperone or as glutathione-independent glyoxalase. To elucidate the role played by this protein in budding yeast cells, we investigated its involvement in the protection against diverse environmental stresses. Our study revealed that HSP31 gene expression is controlled by multiple transcription factors, including Yap1p, Cad1p, Msn2p, Msn4p, Haa1p and Hsf1p. These transcription factors mediate the HSP31 promoter responses to oxidative, osmotic and thermal stresses, to potentially toxic products of glycolysis, such as methylglyoxal and acetic acid, and to the diauxic shift. We also demonstrated that the absence of the HSP31 gene sensitizes cells to these stressors. Overproduction of Hsp31p and its homologue Hsp32p rescued the sensitivity of glo1Δ cells to methylglyoxal. Hsp31p also reversed the increased sensitivity of the ald6Δ strain to acetic acid. Since Hsp31p glyoxalase III coexists in S. cerevisiae cells with thousand-fold more potent glyoxalase I/II system, its biological purpose requires substantiation. We postulate that S. cerevisiae Hsp31p may have broader substrate specificity than previously proposed and is able to eliminate various toxic products of glycolysis. Alternatively, Hsp31p might be effective under high concentration of exogenous methylglyoxal present in some natural environmental niches populated by budding yeast, when glyoxalase I/II system capacity is saturated.

Keywords: Acetic acid; Environmental stress; Ethanol; Fermentation; Methylglyoxal; Saccharomyces cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / toxicity
  • Base Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Ethanol / toxicity
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Promoter Regions, Genetic
  • Protein Deglycase DJ-1 / genetics*
  • Protein Deglycase DJ-1 / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Pyruvaldehyde / toxicity
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Stress, Physiological*
  • Substrate Specificity
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • CAD1 protein, S cerevisiae
  • DNA-Binding Proteins
  • HSF1 protein, S cerevisiae
  • Haa1 protein, S cerevisiae
  • Heat-Shock Proteins
  • MSN2 protein, S cerevisiae
  • MSN4 protein, S cerevisiae
  • Protein Isoforms
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • YAP1 protein, S cerevisiae
  • Ethanol
  • Pyruvaldehyde
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Acetic Acid