Cell death at the millennium. Implications for liver diseases

Abstract

Cell death occurs by apoptosis or necrosis. Although these are morphologically distinct, they share similar initiating events (death receptor ligation, chemicals, drug hypoxia, oxidative stress), and usually involve the participation of mitochondria. The ultimate shape of cell death depends on the extent of functional collapse of mitochondria, which either leads to a rapid loss of ATP, swelling and lysis, or a more selective release of cytochrome c in the presence of sufficient ATP to activate executioner caspases, leading to the development of apoptosis. Apoptosis and necrosis participate in the pathogenesis of most liver diseases. Therapies targeting the death receptors, initiator caspases and mitochondria show potential promise in various liver disease, whereas targeting inhibition of executioner caspases may rapidly or in delayed fashion switch from apoptotic to necrotic cell death.