TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in <i>Saccharomyces cerevisiae</i>.

ABSTRACT: Cells counter accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER) through activation of the Unfolded Protein Response (UPR). Small molecules termed chemical chaperones can promote protein folding to alleviate ER stress. The bile acid tauroursodeoxycholic acid (TUDCA) has been described as a chemical chaperone. While promising in models of protein folding diseases, TUDCA's mechanism of action remains unclear. Here, we found TUDCA can rescue growth of yeast treated with the ER stressor tunicamycin (Tm), even in the absence of a functional UPR. In contrast, TUDCA failed to rescue growth on other ER stressors. Nor could TUDCA attenuate chronic UPR associated with specific gene deletions or overexpression of a misfolded mutant secretory protein. Neither pretreatment w

SUBMITTER: Chadwick SR 

PROVIDER: S-EPMC11809307 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature