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Published on: April 18, 2016
Sorbic acid prevents tunicamycin-induced endoplasmic reticulum stress and Ire1-Hac1 pathway activation in
Yuki Namekata1, Yukio Kimata2, Shingo Izawa1
1Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki Hashikami-cho 1, Kyoto 606-8585, Japan.
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.
Insights
Sorbic acid, a food preservative, does not disrupt the endoplasmic reticulum (ER) in yeast. It unexpectedly prevents ER stress and the unfolded protein response (UPR) induced by tunicamycin.
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Sorbic acid is a common food preservative with known fungistatic properties.
- The precise mechanisms underlying sorbic acid's fungistatic effects are not fully understood.
- Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are critical cellular defense mechanisms.
Purpose of the Study:
- To investigate the effects of sorbic acid on yeast endoplasmic reticulum (ER) homeostasis.
- To elucidate the interaction between sorbic acid and tunicamycin-induced ER stress and UPR.
- To clarify the role of the ER in sorbic acid's fungistatic mechanism.
Main Methods:
- Treatment of yeast with sorbic acid and acetic acid at fungistatic concentrations.
- Assessment of ER homeostasis and stress markers.
- Investigation of the Ire1-Hac1 pathway activation in response to tunicamycin and sorbic acid co-treatment.
Main Results:
- Fungistatic concentrations of sorbic acid did not disrupt ER homeostasis in yeast.
- Unlike acetic acid, sorbic acid did not induce ER stress.
- Sorbic acid pre-treatment or co-treatment prevented tunicamycin-induced ER stress and UPR activation.
- Sorbic acid inhibited the Ire1-Hac1 pathway but could not suppress an established UPR.
Conclusions:
- ER disturbance is unlikely to be the primary mechanism of sorbic acid's fungistatic action.
- Sorbic acid interferes with the induction of ER stress and UPR by tunicamycin.
- These findings offer novel insights into sorbic acid's physiological impact on yeast ER and tunicamycin's mechanism.
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