The Shape of Cell Death

Abstract

Cell death, a scheduled event during development and tissue turnover, or the ultimate consequence of toxic or pathologic insults seems to involve a relatively limited number of execution pathways. This reflects the evolution of an organized sequence of events perhaps converging onto final common pathways that are used to dispose of unwanted or injured cells. In many cases, the ordered execution of this internal death program leads to typical morphological and biochemical changes that have been termed apoptosis. Apoptosis, often equated with developmental or programmed cell death, has been opposed to unscheduled or accidental cell lysis/necrosis. However, increasing evidence suggests that the two forms of cell demise share similar characteristics, at least in the signaling and early progression phase. Recent studies have shown that, when the intensity of the insult is very high and/or when ATP generation is deficient, cells fail to execute the ordered changes ensuing in apoptosis. Then cell lysis/necrosis supervenes before the processes leading to nuclear condensation and exposure of surface molecules can be completed. Thus, apoptosis and necrosis seem to represent only different shapes of cell demise, resulting from a more or less complete execution of the internal death program.