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. Author manuscript; available in PMC: 2014 Jul 30.
Published in final edited form as: N Engl J Med. 2014 Jan 30;370(5):455–465. doi: 10.1056/NEJMra1310050

Figure 1. Programmed cell death is mediated by apoptosis or regulated necrosis.

Figure 1

The term programmed cell death was widely used synonymously with apoptosis until necrotic cell death was demonstrated to depend on genetically defined signaling pathways. Whereas the role of caspase-mediated apoptosis in diseases has been revealed in detail over the last three decades, the contribution of regulated necrosis to the pathophysiology of diseases was investigated only recently. Pathways of regulated necrosis include necroptosis, dependent on RIPK3, and regulated necrosis mediated by mitochondrial permeability transition (MPT) which involves cyclophilin D-dependent opening of the mitochondrial permeability transition pore. Whereas MPT and necroptosis have been demonstrated to represent two distinct pathways, other emerging signaling cascades of regulated necrosis have been described, but it remains currently unclear to what extent such pathways may have overlapping mechanisms.