Endocytosis in Saccharomyces cerevisiae is inhibited by concentrations of
ethanol of 2 to 6% (vol/vol), which are lower than concentrations commonly present in its natural habitats. In spite of this inhibition, endocytosis takes place under enological conditions when high concentrations of
ethanol are present. Therefore, it seems that yeast has developed some means to circumvent the inhibition. In this work we have investigated this possibility. We identified two stress conditions under which endocytosis was resistant to inhibition by
ethanol: fermentation during
nitrogen starvation and growth on nonfermentable substrates. Under these conditions, yeast accumulates stress protectors, primarily
trehalose and Hsp104, a
protein required for yeast to survive
ethanol stress. We found the following. (i) The appearance of
ethanol resistance was accompanied by
trehalose accumulation. (ii) Mutant cells unable to synthesize
trehalose also were unable to develop resistance. (iii) Mutant cells that accumulated
trehalose during growth on
sugars were resistant to
ethanol even under this nonstressing condition. (iv) Mutant cells unable to synthesize Hsp104 were able to develop resistance. We conclude that
trehalose is the major factor in the protection of endocytosis from
ethanol. Our results suggest another important physiological role for
trehalose in yeast.