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.

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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