Quantitative proteomics identifies Ola1p as a positive regulator of heat shock response in Saccharomyces cerevisiae

ABSTRACT: Ola1 is implicated in various stress response pathways, as well as in cancer and tumor progression. However, Ola1p functions are divergent between species and still remain poorly understood. Here, we studied the role of Ola1p in the heat shock response in Saccharomyces cerevisiae. We show that deletion of OLA1 results in higher levels of proteins with protective functions for proteome stability under heat stress. We found that Ola1p enriches in detergent-resistant protein aggregates during heat stress. In heat-stressed yeast cells, it rapidly forms assemblies that localize to stress granules. In vitro, Ola1p assembly is protein autonomous and coincides with structural rearrangements that occur at similar temperatures and pH values seen in cells. We further observed that deletion of OLA1 leads to increased ubiquitination of protein aggregates formed during heat stress. Upon stress relief, central factors for protein refolding and the clearance of protein aggregates are synthesized in higher amounts in dola1 cells, whereas global translation reinitiation is decreased in these cells. Our data suggest that Ola1p is a positive factor for stabilizing the misfolded proteome that is sequestered in cytoplasmic stress granules during heat stress and, thereby, enables cells to efficiently restore a functional proteome after stress relief.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Friedel Drepper  

LAB HEAD: Prof. Dr. Bettina Warscheid

PROVIDER: PXD025615 | Pride | 2022-02-17

REPOSITORIES: Pride