Abstract
Apoptosis, or programmed cell death (PCD), is a naturally occurring process of cell suicide that plays a critical role in the development and maintenance of multicellular organisms. It is required for sculpting tissue architecture, for the development of the nervous and immune systems, as a defense against viral pathogens and protection from cancer1–11. Apoptosis is characterized by cellular shrinkage, nuclear condensation, membrane blebbing and fragmentation of the cell into membrane-enclosed vesicles called apoptotic bodies. The apoptotic bodies are rapidly phagocytosed by neighboring cells and macrophages without the release of cytoplasmic contents. This avoids inflammation and autoimmunization with intracellular constituents. Despite the biological importance of apoptosis, its molecular and biochemical basis remains obscure. The most important information about components of the death pathway comes from the study of the nematode worm Caenorhabditis elegans 12–14. The complete cellular lineage of the hermaphrodite form of C. elegans has been established. Of the 1,090 cells generated during development, 131 die by a cell-intrinsic death program. Genetic analysis has identified 14 genes that function in different steps of PCD in C. elegans. Two genes, ced-3 and ced-4, are required for these developmental deaths. If either is inactivated, none of the 131 cells die7. The ced-9 gene antagonizes the function of ced-3 and ced-4 by protecting cells from death7. In ced-9 loss-of-function mutants, cells that normally live undergo PCD early in development, resulting in embryonic lethality. Thus, ced-9 is necessary for the survival of most cells and presumably ced-9 accomplishes this by suppressing the cell death program7. Several recent discoveries have shed light on the function of the C. elegans cell-death genes and, more importantly, have shown that they have mammalian counterparts with similar functions. The machinery controlling cell viability and cell death appears to be highly conserved through evolution and is briefly reviewed below.
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Dixit, V.M. (1996). Role of Ice-Proteases in Apoptosis. In: Gupta, S., Cohen, J.J. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VI. Advances in Experimental Medicine and Biology, vol 406. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0274-0_11
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