The unfolded protein response alongside the diauxic shift of yeast cells and its involvement in mitochondria enlargement

Sci Rep. 2019 Sep 4;9(1):12780. doi: 10.1038/s41598-019-49146-5.


Upon dysfunction of the endoplasmic reticulum (ER), eukaryotic cells evoke the unfolded protein response (UPR), which, in yeast Saccharomyces cerevisaie cells, is promoted by the ER-located transmembrane endoribonuclease Ire1. When activated, Ire1 splices and matures the HAC1 mRNA which encodes a transcription-factor protein that is responsible for the gene induction of the UPR. Here we propose that this signaling pathway is also used in cellular adaptation upon diauxic shift, in which cells shift from fermentative phase (fast growth) to mitochondrial respiration phase (slower growth). Splicing of the HAC1 mRNA was induced upon diauxic shift of cells cultured in glucose-based media or in cells transferred from glucose-based medium to non-fermentable glycerol-based medium. Activation of Ire1 in this situation was not due to ER accumulation of unfolded proteins, and was mediated by reactive oxygen species (ROS), which are byproducts of aerobic respiration. Here we also show that the UPR induced by diauxic shift causes enlargement of the mitochondria, and thus contributes to cellular growth under non-fermentative conditions, in addition to transcriptional induction of the canonical UPR target genes, which includes those encoding ER-located molecular chaperones and protein-folding enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Unfolded Protein Response*


  • Basic-Leucine Zipper Transcription Factors
  • HAC1 protein, S cerevisiae
  • Membrane Glycoproteins
  • Reactive Oxygen Species
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • IRE1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases