Fig. 6.

Unfolded protein response (UPR) is a valuable target in cell death. Protein misfolding or unfolded can occur as a disturbance in ER homeostasis, leading to ER stress. Chemotherapeutic agents, ROS, proteasome inhibitors, and HSP 90 inhibitors as ER stress inducers perturb ER homeostasis differently. If ER stress is not resolved in a timely fashion, unfolded or misfolded proteins accumulate in ER, and UPR triggers cell death via ATF6, PERK and IRE1α mediated signaling pathways. Importantly, fluctuations in ER and mitochondrial Ca²⁺ homeostasis can initiate mitochondrial-mediated cell death. UPR unfolded protein response, ROS reactive oxygen species, HSP 90 heat shock protein 90, mPTP mitochondrial permeability transition pore, CHOP C/EBP homologous protein, ATF6 p50ATF60, ATF4 transcription factor 4, TRAF2 TNF receptor-associated factor 2, ASK1 apoptosis signal-regulating kinase 1, JNK c-jun N-terminal kinase