Fig. 3: Molecular mechanism of NLRP3-dependent PANoptosis.
From: Diverse functions of NLRP3 inflammasome in PANoptosis and diseases
When stimuli such as microbial infections or changes in cellular homeostasis are detected by intracellular sensor molecules, including ZBP1, AIM2, RIPK1, NLRP12, and NLRC5, certain cell death molecules are recruited to form a PANoptosome. NLRP3 is mainly involved in the formation of the ZBP1-PANoptosome (ZBP1, NLRP3, ASC, Caspase-1, RIPK3, Caspase8, and Caspase 6), the RIPK1-PANoptosome (RIPK1, NLRP3, ASC, Caspase 1, RIPK3, and Caspase8), the NLRP12-PANoptosome (NLRP12, NLRP3, ASC, Caspase 1, RIPK3, and Caspase8) and the NLRC5-PANoptosome (NLRC5, NLRP3, ASC, NLRP12, RIPK3, and Caspase8). These PANoptosomes further induce downstream Caspase 1 activation-mediated GSDMD cleavage, Caspase 3/7 activation-mediated GSDME cleavage, and RIPK3-mediated MLKL phosphorylation, promoting membrane pore formation and PANoptosis.
