Endoplasmic reticulum: Stress, signalling and apoptosis

Abstract

The synthesis, folding and processing of the secretory/ membrane proteins by the endoplasmic reticulum (ER) requires the functioning of ER chaperones, maintenance of ER calcium pools, and an oxidative environment. Disruption of the ER functioning elicits an adaptive signalling cascade called the unfolded protein response (UPR). UPR is triggered by the activation of ER transmembrane proteins and modulated by ER chaperones. It comprises of general inhibition in protein synthesis, induction of ER chaperones, and components of ER-associated protein degradation. UPR is implicated in development, disease and virus infection. Incessant ER stress, through unknown mechanism(s) bolsters the proapoptotic potential of the UPR with a subsequent decline in the adaptation capabilities and initiates cell death. This review highlights the mammalian UPR signalling pathways in general, and the major players implicated in ER stress-induced apoptosis.