[Endoplasmic reticulum-mediated integrated stress response]

Integrated stress response (ISR) is a high conserved cell adaptive response, which is induced by oxidative stress, deprivation of acid aminos, and endoplasmic reticulum (ER) stress through eukaryotic translation initiator factor 2alpha (eIF2alpha) pathway. Recently, it is reported that protein kinase R-like ER kinase (PERK) , the upstream of eIF2alpha is the key molecule in ISR. PERK regulates protein synthesis, folding, autophagy and apoptosis through cross-talking with inositol-requiring enzyme-1 (IRE1) and activating transcription factor 6 (ATF6), another two signaling pathways in ER stress. We reviewed the factors induced ISR and its signaling pathways, summarized the physiological and pathophysiological role of endoplasmic reticulum-mediated integrated stress response.