UPR deficiency leads to poor growth, aneuploidy, and a trade-off between ER and general proteostasis in yeast.

ABSTRACT: The unfolded protein response (UPR) was discovered in budding yeast as a mechanism that allows cells to adapt to endoplasmic reticulum (ER) stressors. Although the UPR is not thought to be necessary for cellular fitness of wild-type cells in the absence of stress, we found that UPR deficiency led to poor growth in cycling mitotic yeast cells. This led to pervasive adaptive aneuploidy of specific chromosomes that was seen in divergent strain backgrounds, indicating an important basal role for this pathway that was missed by studies of the most common laboratory-derived strains. Aneuploid UPR-deficient cells grew better than euploid UPR-deficient cells but exhibited heightened general proteostatic stress, a hallmark of aneuploidy in wild-type cells. Modulation of key genes involved in ER pro

SUBMITTER: Bartolutti C 

PROVIDER: S-EPMC12667388 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature