Exploiting different ways to die
- Howard Hughes Medical Institute and Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey 08854, USA
This extract was created in the absence of an abstract.
Major modes of cell death
Far from a mere end point, cell death is an essential and highly orchestrated process. Developmental cell death is recognized to play a major role in morphogenesis and tissue sculpting, whereas cell death in mature organisms is essential for tissue homeostasis, wound healing, and elimination of infectious pathogens. Conversely, defective regulation or execution of cell death is also widely recognized as the basis for a spectrum of diseases, including many major human health foes such as diabetes, degenerative disorders, and cancer. Three major types of cell death have been distinguished, all of which contribute to proper development and well-being: apoptosis, autophagy, and necrosis.
Apoptosis is an ordered cell death process in which the entire cell is dismantled within the context of membrane-enclosed vesicles that are recognized and engulfed by phagocytes, thereby preventing release of intracellular components from the dying cells. Studies from many organisms, including Caenorhabditis elegans, Drosophila, and mammals have illustrated that apoptosis is a sophisticated, genetically controlled process integrating a common set of death effectors with a wide range of different stimuli. During development, apoptosis eliminates cells as part of normal morphogenesis, as well as those that incur cellular or genetic damage. In mature organisms, apoptosis ensures proper tissue homeostasis, contributing to normal cell turnover and eliminating both dividing cells with genome damage and cells infected with pathogens, both of which would compromise proper homeostasis. In cells committed to die, proper cell dismantling is carried out by the concerted action of a set of cysteine proteases called caspases. The decision of whether to commit to death is controlled by a large group of regulatory proteins, including the BCL-2 family, inhibitors of apoptosis proteins, and components of death receptor signaling systems. These proteins, in turn, are regulated by the signaling cascades that transduce environmental and cell damage stimuli …
