Mammalian cells have developed the means for efficient and ordered self-removal from tissues, termed programmed cell death. Of the pathways encompassed in this class, apoptosis is the most highly characterized mode of cell death (1). Apoptosis is a physiological, energy-dependent process whereby a cell systematically breaks down its intra-cellular components and signals patrolling immune cells to engulf the dying cell (1–3). This process prevents the release of the cell's enzymatic or infectious contents and allows for recycling of valuable materials. This process is in contrast to the accidental mode of cell death, termed necrosis, where cells with ruptured cell membranes leach their cellular contents into surrounding healthy tissue, causing damage. In contrast, programmed cell death describes a class of well-conserved cellular mechanisms that provides a way for degradation of diseased, damaged, or unnecessary cells in a non-inflammatory manner (4,5).

Apoptosis has been broadly described as either intrinsically (mitochondrial initiation) or extrinsically (plasma membrane receptor initiation) mediated during the initiation phase of the cell-death process (6,7). Specific proteases and multi-meric complexes are attributed to each of these pathways, although both routes end in the activation of common downstream mediators (8). For the extrinsic pathway, the binding of ligands to death receptors on the plasma membrane leads to the formation of death-inducing signaling complexes (DISCs) that then go on to signal other apoptotic events. Specifics of the extrinsic mode of apoptosis are covered in Chapter 30. In contrast, the intrinsic pathway is initiated by an intra-cellular event, such as mitochondrial and/or DNA damage (9,10). Other cell-death pathways have been suggested that do not fit into either the extrinsic or intrinsic paradigm (11). These events, however, are still classified as apoptosis rather than necrosis because of certain characteristic apoptotic features being present.