Diverse stimuli from inside or outside the cell can cause apoptosis. Inflammatory cytokines (e.g., TNFα) may continually induce the activation of caspase-8, caspase-3, and DNA fragmentation through membrane receptors. This apoptotic pathway, called the extrinsic pathway, is a direct activation of caspases. Intracellular metabolic disturbances or excess reactive oxygen species can hurt mitochondria and result in cytochrome c release and caspase-9 activation. The activated caspase-9 further stimulates caspase-3 activation and apoptosis. Because this type of apoptosis is from mitochondrion-mediated activation of caspases, it is thus named mitochondrial-dependent pathway or mitochondrial pathway. Sometimes, it is also called indirect pathway or intrinsic pathway. Mitochondrial dependent pathway is different from extrinsic apoptotic pathway, but two pathways are not mutually exclusive in liver. The mitochondrial pathway is very important during hepatic apoptosis, which is often required to amplify the relatively weak death receptor-induced apoptotic signal. Apoptotic causative factors are able to activate survival signals against cell death as well.