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

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 HAC 1 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 HAC 1 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.

A Quantitative Analysis of Cellular Lipid Compositions During Acute Proteotoxic ER Stress Reveals Specificity in the Production of Asymmetric Lipids

“…Specifically, DTT was used at a concentration of 8 mM and 2 mM, while TM was used at a concentration of 1.0 μg/ml and 1.5 μg/ml in rich and synthetic medium, respectively. Notably, 8 mM of DTT has previously been used to study ER membrane expansion in stressed cells, while 1–2 μg/ml of TM are known to reorganize Golgi traffic and mitochondrial enlargement by activating the UPR ( Bernales et al, 2007 ; Schuck et al, 2009 ; Hsu et al, 2016 ; Tran et al, 2019 ).…”

Improving the catalytic performance of Pichia pastoris whole-cell biocatalysts by fermentation process

“…As a transcription factor, HAC1 could alleviate ER stress, and trigger unfolded protein response (UPR), which would reduce ROS production. 56,57 Compared to Pp-S 2 U 4 , a 69% catalytic activity decrease and reduced ROS levels were both observed in the HAC1-expressing strain (Fig. 6c and d).…”

The unfolded protein response of the endoplasmic reticulum supports mitochondrial biogenesis by buffering non-imported proteins

“…Our findings add to a significant body of observations linking the stress responses and homeostasis mechanisms of mitochondria and ER 97 . Several processes connect mitochondrial and ER homeostasis in the context of stress: the flux of lipids between mitochondrial and ER membranes 98 ; the generation of ATP as well as reactive oxygen species by the respiratory chain 99,100 ; the transport of calcium 16,101 ; or the availability of building blocks for glycosylation of secretory proteins, provided by mitochondrial carbohydrate metabolism 102 . We propose that mitochondria and ER are also linked in the management of mitochondrial biogenesis.…”