Skip to main content
. 2019 Aug 8;4(15):e128834. doi: 10.1172/jci.insight.128834

Figure 1. Modes of cell death.

Figure 1

Cell death pathways include those that are regulated by genetic programs, which are designated regulated cell death (RCD), and those that are not regulated, which are designated accidental cell death (ACD). Apoptosis is a form of RCD that requires activation of caspases, leading to DNA fragmentation. The initiation of apoptosis may be receptor dependent (extrinsic pathway) or triggered by injurious stimuli (intrinsic pathway), resulting in mitochondrial dysfunction. Apoptosis culminates in nonlytic cell death, which is noninflammatory. Pyroptosis is a form of lytic cell death that occurs in inflammatory cells in response to proinflammatory stimuli. A cardinal feature of pyroptosis is the requirement for inflammasome-dependent caspase-1 activation, which regulates the maturation and secretion of proinflammatory cytokines. Pyroptosis occurs as the result of gasdermin D–regulated (GSDMD-regulated) membranous pore formation and features cytoplasmic swelling and cytosolic content leakage. Necroptosis represents a form of RCD that is activated by RIPK1 and requires RIPK3-dependent phosphorylation of MLKL. MLKL oligomerization results in plasma membrane rupture, leading to a lytic form of cell death associated with release of DAMPs. Ferroptosis is an RCD mode that is distinct from necroptosis. In ferroptosis, iron-dependent lipid peroxidation causes lytic cell death, which can be inhibited by glutathione peroxidase 4 (GPX4). Necrosis is a lytic form of ACD that results in DAMP release and propagation of inflammation. A variant of necrosis that involves mitochondrial permeability transition (MPT) has also been described. DAMPs, damage-associated molecular patterns; MLKL, mixed-lineage kinase domain–like pseudokinase; NLRP3, nucleotide-binding oligomerization domain–, leucine rich repeat–, and pyrin domain–containing protein 3; PYCARD, PYRIN-PAAD-DAPIN domain– and C-terminal caspase-recruitment domain–containing protein; RIPK1, receptor-interacting protein kinase 1; RIPK3, receptor-interacting protein kinase 3.