Abstract: Caspases (cysteine aspartate-specific proteases) coordinate the dismantling of the cell that takes place during apoptosis and activate the membrane changes that trigger recognition and removal of apoptotic cells by phagocytes. The functional outcome of caspase-dependent proteolysis during apoptosis appears to be the minimization of inflammation, rather than achieving death of the cell per se. The latter view is based on the fact that a great many of the stimuli that promote apoptosis do so by promoting mitochondrial permeabilization, upstream of caspase activation, to release cytochrome c and other mitochondrial intermembrane space constituents. Cytosolic cytochrome c promotes assembly of the Apaf-1/caspase-9 apoptosome, which promotes activation of a cascade of additional caspases that cooperate to cleave hundreds of proteins during apoptosis. Because caspase activation frequently occurs downstream of mitochondrial permeabilization, cells fail to survive even if caspase activation is blocked. Instead, such cells die via necrosis where intracellular contents are released and inflammation is induced. In contrast, where caspases are activated during cell death, dying cells are recognized and removed by neighboring cells and resident macrophages prior to cell rupture, thereby minimizing inflammation. Thus, caspases function in apoptosis predominantly to suppress inflammation, rather than to terminate cell viability.
Publication Year: 2014
Publication Date: 2014-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 34
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