Apoptosis occurs via two molecular pathways, extrinsic and intrinsic. The extrinsic pathway involves death ligand-induced activation of receptors, resulting in the formation of the death complex. The intrinsic pathway is activated by cellular stress and mitochondrial dysfunction. ER stress can induce apoptosis through JNK and CHOP, which activate the proapoptotic protein Bax, leading to mitochondrial dysfunction. Both apoptotic pathways activate intracellular proteases, the caspases, that cleave cell components in an organized way. The engulfment of the resulting apoptotic bodies by Kupffer cells promotes hepatic fibrosis and inflammation through the activation of stellate cells and the release of cytokines.
CHOP: C/EBP homologous protein; Cyto c: Cytochrome c; ER: Endoplasmic reticulum; FasL: Fas ligand; PERK: PKR-like ER kinase; TRAIL: TNF-related apoptosis-inducing ligand.