Abstract
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.
Highlights
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 Ire[1]
This research was initiated by our finding that a considerable but transient UPR is observed upon long-time culture of yeast cells in standard synthetic dextrose (SD) medium
In the present study, we cultured yeast cells in the two most commonly used media, yeast extract-peptone-dextrose (YPD) and SD, for long duration and noticed that the UPR is transiently induced upon diauxic shift (Figs 1, S1 and S4)
Summary
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 Ire[1]. We show that the UPR induced by diauxic shift causes enlargement of the mitochondria, and contributes to cellular growth under non-fermentative conditions, in addition to transcriptional induction of the canonical. Accumulation of unfolded proteins in the ER, which is tightly linked to dysfunction of the ER, is called ER stress, and triggers the unfolded protein response (UPR) in eukaryotic cells. In ER-stressed Saccharomyces cerevisiae (hereafter called yeast) cells, the HAC1 mRNA is spliced by activated Ire[1] molecules and translated into a transcription-factor protein, which functions in UPR transcriptional induction. According to previous reports by us and others[7,8,9], the self-associated forms of yeast Ire[1] and IRE1α (the major version of the mammalian Ire[1] paralogues) directly capture unfolded proteins accumulated in the ER for their high-order oligomerization and full activation
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