An ER-accumulated mutant of yeast Pma1 causes membrane-related stress to induce the unfolded protein response.

Upon dysfunction of the endoplasmic reticulum (ER), namely ER stress, eukaryotic cells provoke the unfolded protein response (UPR), which is triggered by ER stress sensors including Ire1. While the ER luminal domain of Ire1 is known to directly recognize misfolded soluble proteins accumulated in the ER, the transmembrane domain of Ire1 is involved in its self-association and activation upon membrane lipid-related abnormalities, which are so-called lipid bilayer stress (LBS). Here we inquired how the ER accumulation of misfolded transmembrane proteins induces the UPR.

Aeration mitigates endoplasmic reticulum stress in even without mitochondrial respiration.

is a facultative anaerobic organism that grows well under both aerobic and hypoxic conditions in media containing abundant fermentable nutrients such as glucose. In order to deeply understand the physiological dependence of on aeration, we checked endoplasmic reticulum (ER)-stress status by monitoring the splicing of mRNA, which is promoted by the ER stress-sensor protein, Ire1. -mRNA splicing that was caused by conventional ER-stressing agents, including low concentrations of dithiothreitol (DTT), was more potent in hypoxic cultures than in aerated cultures.