ER stress and the UPR Sample Clauses

ER stress and the UPR. ‌ The ER functions in the production of lipids, proteins and as a store for Ca2+ (Xxxxx et al., 2013). Alterations in protein homeostasis and folding can lead to an impaired ER function causing ER stress (Xxxxxxxx and Xxxxxxxx, 2003; Xxxxx et al., 2013). Several conditions can lead to ER stress: a high demand for protein secretion, viral infection, oxygen and nutrient deprivation and missense mutations (Xxx, 1992; Xxxx et al., 2002; Xxxxxxx et al., 2005; Xxxxx et al., 2005; Xxxxxx et al., 2006; Xxxxxxxxxxxx et al., 2008). Even under normal conditions about 30 % of newly synthesised proteins are misfolded (Xxxxxxxx et al., 2000). The majority is re-folded into their correct structure but some cannot be re- folded and these are marked for degradation but can also accumulate and cause ER stress (Xxxxxxxx et al., 1999). Restoration of ER homeostasis after ER stress is crucial for the survival of the cell. The ER has an adaptive response system that is triggered to deal with an overload of unfolded proteins called the UPR. There are sensors in the ER lumen that can detect disturbances in protein folding homeostasis and signal to the nucleus to trigger a compensatory response (Bravo et al., 2013). The stress response system has four distinct elements: