Fungistatic Effect of Sorbic Acid on Yeast Cells Via Translational Repression Involving Eif2α Phosphorylation and Formation of Ded1- and Eif2b-Granules

Sorbic acid is a lipophilic weak acid with fungistatic activity, and it has been widely used as a food preservative, along with its potassium and calcium salts. Although the fungistatic effect of sorbic acid is thought to be primarily due to acidification within fungal cells, the detailed fungistatic mechanism remains unclear. We investigated the effects of sorbic acid on yeast translation in Saccharomyces cerevisiae. At sublethal concentrations (2-4 mM), sorbic acid quickly repressed translation. Conversely, removal of sorbic acid restored translation activity, indicating that the sorbic acid-induced translational repression is reversible. Pronounced translational repression induced by various stress conditions or nutrient starvation is often accompanied by eIF2 α phosphorylation, eIF2B-body and stress granule (SG) formation, and the sequestration of Ded1 (which plays a role in translation initiation as a DEAD-box RNA helicase) into SGs. We found that sorbic acid stress also induces eIF2 α phosphorylation and the sequestration of Ded1 into SGs. In contrast, sorbic acid stress induced the formation of not eIF2B bodies but eIF2B granules, which colocalized with SGs. These results suggest that the functional arrest of translation-related factors, including eIF2 α , eIF2B, and Ded1, correlates strongly with the translational repression in the presence of sorbic acid. Notably, Gcn2 deficiency delayed translational repression and SG formation, and significantly suppressed eIF2B granule formation, suggesting the involvement of Gcn2 in these stress responses during sorbic acid stress. Our findings provide new insights into the physiological effects of sorbic acid on yeast cells, specifically regarding the regulation of translation-related factors.