Figure 2
Outlines of the signal transduction pathways leading to plasma membrane changes in apoptosis (including secondary necrosis), necroptosis, and pyroptosis. (A) Apoptosis can be initiated by either intrinsic or extrinsic pathway. Caspase-3 activation resulting from either pathway cleaves ROCK1 to promote plasma membrane blebbing, followed by generation of apoptotic bodies. Caspase-3 can also cleave DFNA5 to generate the DFNA5 N-terminal fragment, which forms oligomers and translocates to the plasma membrane, leading to its rupture by the formation of non-selective pores and finally secondary necrosis. (B) In the necroptotic pathway, various external death ligands can initiate necrosome assembly. Once in the necrosome, RIP3 is autophosphorylated. Phosphorylated RIP3 recruits and phosphorylates MLKL, leading to MLKL oligomerization and translocation to the plasma membrane. MLKL oligomers execute necroptosis by generating cation channels, causing plasma membrane rupture. (C) Pyroptotic stimulation elicits inflammasome formation and subsequent caspase-1 activation. Activated caspase-1 cleaves GSDMD, generating the GSDMD N-terminal fragment, which oligomerizes and translocates to the plasma membrane and causes plasma membrane rupture via non-selective pore formation.
