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(Un)folding mechanisms of adaptation to ER stress: lessons from aneuploidy

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Abstract

During stress, accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers activation of the adaptive mechanisms that restore protein homeostasis. One mechanism that eukaryotic cells use to respond to ER stress is through activation of the unfolded protein response (UPR) signaling pathway, which initiates degradation of misfolded proteins and leads to inhibition of translation and increased expression of chaperones and oxidative folding components that enhance ER protein folding capacity. However, the mechanisms of adaptation to ER stress are not limited to the UPR. Using yeast Saccharomyces cerevisiae, we recently discovered that the protein folding burden in the ER can be alleviated in a UPR-independent manner through duplication of whole chromosomes containing ER stress-protective genes. Here we discuss our findings and their implication to our understanding of the mechanisms by which cells respond to protein misfolding in the ER.

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Acknowledgements

This work was supported by the National Institutes of Health Grant AG054566 (to VML). This research was conducted while VML was an AFAR Research Grant recipient from the American Federation for Aging Research.

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Correspondence to Vyacheslav M. Labunskyy.

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Communicated by M. Kupiec.

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Beaupere, C., Labunskyy, V.M. (Un)folding mechanisms of adaptation to ER stress: lessons from aneuploidy. Curr Genet 65, 467–471 (2019). https://doi.org/10.1007/s00294-018-0914-9

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  • DOI: https://doi.org/10.1007/s00294-018-0914-9

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