Fig. 3: Molecular mechanisms of necroptosis.

TNF ligation or LPS stimulation results in activation of NF-κB signaling. Inactivation of NF-κB signaling or engagement of death receptors triggers the assembly of an apoptosis-inducing complex consisting of FADD, caspase-8, and RIPK1. When caspase-8 is inhibited, RIPK1 and RIPK3 form necrosomes through homotypic interactions with RHIM, resulting in phosphorylation of MLKL. Phosphorylated MLKL undergoes oligomerization and induces membrane rupture.