How cells die: Apoptosis pathways

Abstract

Generally speaking, there are 2 types of cell death: apoptosis and necrosis. Necrotic cell death is considered an accidental type of death, caused by gross cell injury, and results in the death of groups of cells within a tissue. In contrast, apoptotic cell death may be induced or is preprogrammed into the cell (eg, during development) and results in the death of the individual cells. Apoptotic cells may be characterized by specific morphologic and biochemical changes orchestrated by a family of cysteine proteases known as caspases. At the molecular level, apoptosis is tightly regulated. There are 2 main pathways to apoptotic cell death. One involves the interaction of a death receptor, such as the TNF receptor-1 or the Fas receptor with its ligand, and the second pathway depends on the participation of mitochondria. Proapoptotic and antiapoptotic members of the Bcl-2 family regulate the mitochondrial pathway. The end result of either pathway is caspase activation and the cleavage of specific cellular substrates, resulting in the morphologic and biochemical changes associated with the apoptotic phenotype.