The pantheon of the fallen: why are there so many forms of cell death?

Abstract

Cells die by various mechanisms, only some of which have been elucidated in detail. Numerous 'active' forms of cell death exist in which the cell participates in its own death, including apoptosis, programmed necrosis, mitotic catastrophe, and the recently described ferroptosis. Here, we attempt to explain why there are so many different forms of cell death, and propose a distinction between active death that constitutes 'suicide' versus 'sabotage'.

Figure 1

Active and passive cell deaths. Passive cell death occurs when a vital cellular function is directly damaged or inhibited, thus killing the cell. Active cell death can be of two forms. One can be classified as cellular `suicide,' in which a pathway that is specialized for cell death signaling is engaged. The best example of this is apoptosis, although there may be others. Alternatively, cell death can be active -- that is, a cell participates in its own demise -- if cellular processes are `sabotaged' such that the continuation of the process is lethal. This distinction may prove useful in understanding why there appear to be so many ways that cells can actively die (images from iStockphoto.com).