More than one way to go

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Abstract
Dramatic changes accompany the death of cells. Attempts to align these changes into cognate groups and identify the mechanisms responsible for them have led to substantial and sometimes surprising insights into cell biology. One such constellation of structural and functional changes is associated with apoptosis (a death process found in development, atrophy, the targets of cell killing by the immune system, and the response of many cell types to relatively low concentrations of many xenobiotics; ref. 1). Several of the events of apoptosis can be traced to activation of intracellular caspases, a group of cysteine proteases with aspartate-directed cleavage preference (2). Cells, and indeed whole animals, rendered deficient in certain caspases through contrived, germ-line knockout are now available, as are potent, broad-spectrum caspase inhibitors. These resources have revealed that death processes exist that are independent of caspase proteolysis and demonstrate a phenotype unlike that of apoptosis. In a recent paper in PNAS, Sperandio et al. (3) present a striking picture of one of these death processes. Their observations are exciting because they may highlight a mechanism of internally programmed cell death that often exists in parallel with apoptosis but may be subject to different controls. In particular, this death process, which the authors name paraptosis, may be relevant to the pathogenesis of central nervous system degenerations. The observations of Sperandio et al. are exciting because they may highlight a mechanism of internally programmed cell death that often exists in parallel with apoptosis but may be subject to different controls. Several of the most obvious features of apoptosis are found in the nucleus. Chromatin condenses, initially in a circumferential pattern, but thereafter throughout the whole nucleus, which becomes shrunken and often separates to several spherical bodies. In step with these appearances, DNA is cleaved, first to large chromatin domains of …