Sorbic acid prevents tunicamycin-induced endoplasmic reticulum stress and Ire1–Hac1 pathway activation in Saccharomyces cerevisiae

Abstract

Sorbic acid is a widely used food preservative recognized for its potent fungistatic effects, yet its specific mechanisms of action remain poorly understood. While investigating its effects on yeast organelles, we found that fungistatic concentrations of sorbic acid do not disturb homeostasis within the endoplasmic reticulum (ER). This contrasts with acetic acid, which induces ER stress despite having a similar dissociation constant, suggesting that ER disturbance is unlikely to be central to the fungistatic mechanism of sorbic acid. Unexpectedly, we discovered that sorbic acid prevents the induction of ER stress and the unfolded protein response (UPR) by tunicamycin. Sorbic acid abrogates activation of the Ire1–Hac1 pathway when administered prior to or during tunicamycin treatment, although it cannot suppress an already-induced UPR. These findings provide new insights into the physiological effects of sorbic acid on the yeast ER and the mechanism of action of tunicamycin.