Molecular Mechanisms of Cell Death

Cell death is a fundamental pathophysiological process and also an essential event in normal life and development. Although many stimuli cause death of cells, the mode of cell death typically follows one of two patterns. The first is necrosis, or oncosis. Oncotic necrosis is most often the result of profound metabolic disruption and is characterized by cellular swelling leading to plasma membrane rupture with release of intracellular contents. The second pattern is apoptosis, a form of programmed cell death. Apoptosis causes the orderly resorption of individual cells initiated by well-defined pathways involving activation of proteases called caspases. In contrast to necrotic cell death, which typically occurs from adenosine triphosphate (ATP) depletion, apoptosis is an ATP-requiring process. Several distinct organelles (plasma membrane, mitochondrion, nucleus, endoplasmic reticulum, lysosome) give rise to signals that induce cell death. In particular, mitochondrial permeabilization and dysfunction typically develop in both necrosis and apoptosis. In some instances, apoptosis and necrosis share signaling pathways, as occurs in programmed necrosis called necroptosis. In this way, apoptosis and necrosis can represent extreme endpoints on a phenotypic continuum of lost cell viability.