Zinc depletion activates the endoplasmic reticulum-stress sensor Ire1 via pleiotropic mechanisms.

Although zinc deficiency evokes the endoplasmic reticulum (ER)-stress response, the activating mechanism remains obscure. Here we show that in yeast cells, the ER-stress sensor Ire1 was activated upon zinc deficiency. ER-stressing stimuli activating Ire1 are known to include ER accumulation of unfolded proteins and membrane-lipid aberrancy. According to the findings presented here, zinc deficiency causes both types of abnormality.