fig2

Figure 2. The classical pathway of necroptosis. The classical form of necroptosis begins with the binding of TNF-α to TNFR1, initiating the formation of complex I. If the ubiquitylation of RIP1 within complex I is inhibited, it undergoes a transition into complex IIA and complex IIB. When caspase-8 is inactive, complex IIB recruits RIP3 to form the necrosome. Once RIP3 is phosphorylated, it recruits and phosphorylates MLKL, leading to its oligomerization. The oligomerized MLKL is subsequently translocated to the plasma membrane, resulting in necroptosis. MLKL: Mixed lineage kinase domain-like protein; PIR1: receptor-interacting protein 1; RIP3: receptor-interacting protein 3; TNF: tumor necrosis factor; TNFR: TNF receptor; TRADD: TNF-α receptor-associated death domain TRAF: TNFR-associated factor.