Abstract
The unfolded protein response (UPR) is a conserved intracellular signaling pathway that controls transcription of endoplasmic reticulum (ER) homeostasis related genes. Ethanol stress has been recently described as an activator of the UPR response in yeast Saccharomyces cerevisiae, but very little is known about the causes of this activation. Although some authors ensure that the UPR is triggered by the unfolded proteins generated by ethanol in the cell, there are studies which demonstrate that protein denaturation occurs at higher ethanol concentrations than those used to trigger the UPR. Here, we studied UPR after ethanol stress by three different approaches and we concluded that unfolded proteins do not accumulate in the ER under. We also ruled out inositol depletion as an alternative mechanism to activate the UPR under ethanol stress discarding that ethanol effects on the cell decreased inositol levels by different methods. All these data suggest that ethanol, at relatively low concentrations, does not cause unfolded proteins in the yeasts and UPR activation is likely due to other unknown mechanism related with a restructuring of ER membrane due to the effect of ethanol.
Highlights
The generation of essential proteins through the secretory pathway is one of the most important tasks of cells
Our results showed that the doubling time in the cells pre-exposed to 0.2 μg/mL of tunicamycin was significantly lower than in non-pre-exposed cells under ethanol stress (Supplementary Table S1)
When we compared green fluorescent protein (GFP)-Atg8 in the cells treated with a protein-denaturing agent (DTT), we found that 62.5% of the cells had a large number of pre-autophagosomal structures (PASs)/cell (5 ± 2 spots per cell), even within the vacuole, whose lumen showed increased intensity
Summary
The generation of essential proteins through the secretory pathway is one of the most important tasks of cells. The UPR pathway involves an ER membrane sensor that binds unfolded proteins, and undergoes oligomerization and autophosphorylation. This sensor, called Ire1p (inositol responsive element 1), acquires endoribonuclease activity, which promotes the elimination of an intron present in the mRNA of transcription factor Hac1p. This regulator activates the transcription of hundreds of genes and restores proper ER function (Cox and Walter, 1996; Sidrauski and Walter, 1997). The INO1 gene, which encodes a key component of the inositol biosynthetic pathway, is activated to restore lipid levels (Greenberg and Lopes, 1996)
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