Fig. 1

Absent in melanoma 2 (AIM2)-mediated pyroptosis and PANoptosis. AIM2 assembles into the AIM2 inflammasome by recognizing double-stranded DNA and subsequently oligomerizing and binding ASC and procaspase-1. The cleavage of procaspase-1 promotes the maturation of caspase-1. Caspase-1, in turn, promotes the maturation of pro-1β and pro-18 and cleaves gasdermin D (GSDMD) to promote the disruption of cell membranes and the release of IL-1β and IL-18. AIM2 also binds ASC, FADD, RIPK1, RIPK3, caspase-1, caspase-8, and ZBP1 to assemble the PANoptosome and activate downstream effectors, including the apoptosis effectors (caspase-3, -6, and -7), pyroptosis effector (GSDMD), and necroptosis effector (MLKL), thereby promoting PANoptosis. In addition, AIM2 binds caspase-8, caspase-1, and ASC to form a complex, activating caspase-8 and caspase-1, cleaving downstream caspase-3, and ultimately promoting apoptosis. Cleaved caspase-3 inhibits gasdermin D and mediates pyroptosis through gasdermin E. Caspase-1 also activates pyroptosis via gasdermin