Fig. 1.
Pathways of programmed cell death. Apoptosis can be triggered through intrinsic or extrinsic pathways, which can induce caspase-9 activation. As a result, caspase-3 and caspase-7 are cleaved into their active forms and lead to apoptosis. In pyroptosis, canonical inflammasome complexes activate caspase-1, which in turn converts pro–interleukin (IL)-1β and pro–IL-18 into their active forms. Sensing of intracellular lipopolysaccharide (LPS) can activate caspase-11, triggering noncanonical inflammasome. Activated caspase-11 then cleaves gasdermin D (GSDMD) and releases the N-terminal p30 domain, which induces membrane pores. External death inducers can activate receptor-interacting protein kinase 3 (RIPK3), which phosphorylates mixed lineage kinase domain-like (MLKL). Phosphorylated MLKL binds to the plasma membrane and forms the necroptotic pore. Both necroptosis and pyroptosis induce cell membrane rupture, releasing cellular components which may trigger inflammation. BID = BH3-interacting domain death agonist; DAMP = damage associated molecular pattern; PAMP = pathogen associated molecular pattern; tBID = truncated BID; ZBP1 = Z-DNA binding protein 1.