Fig. 1.

Intrinsic pathway and extrinsic pathway of apoptosis include endoplasmic reticulum stress pathway, mitochondrial pathway and death receptor pathway. The endoplasmic reticulum pathway is caused by the excessive activation of UPR indecued by ERS, including IRE1α, PERK/eIF2α/ATF4 and ATF6 pathways, causing the activation of CHOP to induce apoptosis. Mitochondrial pathway is regulated by Bcl-2 protein family. The Bax/Bak complex leads to increased permeability of the mitochondrial membrane, which releases several pro-apoptotic proteins, including Cyt C, and initiates the next step of the caspase-processing cascade, inducing apoptosis. Ca²⁺ in the endoplasmic reticulum pathway is not only involved in the endoplasmic reticulum stress pathway, but also affects the mitochondrial pathway by influencing the Bax complex. The death receptor pathway means that the death ligand binds to the receptor after receiving external death stimulation signals, resulting in its trimerization, activation of downstream caspase-8 and apoptosis