Programmed cell death.
Developmentally programmed cell death in animals is accomplished by the activation of a protease of the caspase family. Caspase activation is an essential feature of apoptosis. In Caenorhabditis elegans, this protease is CED-3, which corresponds to mammalian caspase-3. Caspases comprise a distinct family of cysteine aspartases that are activated by interaction with a co-factor and/or proteolytic processing. Once activated, they cleave targets containing the exposed consensus sequences, including other caspases, protein kinases and structural elements, to achieve the death of the cell. Apoptotic cells undergo a dramatic volume loss accompanied by ionic shifts and cytoplasmic acidification. The cytoskeleton rearranges and the cell membrane undergoes blebbing and phosphatidylserine externalization, thus marking the dying cell for ingestion by phagocytes. In addition to structural changes, mitochondria cease to synthesize ATP, release cytochrome c and other constituents, and lose membrane potential. DNA undergoes endonucleolytic cleavage first into 50-kb fragments, followed by cleavage to oligonucleosomes. Together these biochemical processes achieve the noninflammatory destruction of the cell.
Gottlieb
R A
RA
Division of Hematology, Department of Molecular & Experimental Medicine MEM 220, The Scripps Research Institute, La Jolla, California 92037, USA.