fig1

Figure 1. Mechanism of tumour necrosis factor-α (TNF-α) induced necroptosis. Binding of TNF-α to its receptor results in formation of Complex I. Activation of cIAP and tartrate resistant acid phosphatase activates downstream NF-κB signaling and subsequently promote cell survival. Complex II acts as a switch between apoptosis and necroptosis. Activation of caspase-8 guides the cells to apoptosis. Inhibition of caspase-8 leads to formation of a necrosome. Membrane translocation of phosphrylated MLKL disrupts cell membrane. The mechanisms underlying the lysis of cytoplasmic contents during necrosis are still unclear. DAMPs: damage associated molecular patterns; MLKL: mixed lineage kinase domain-like protein; TNF: tumour necrosis factor; TNFR: tumour necrosis factor receptor; cIAP: calf intestinal alkaline phosphatise; TRADD: tumor necrosis factor receptor associated death domain; TRAF: TNFR-associated factors; RIP1: receptor-interacting protein 1; CYLD: cylindromatosis; Casp8: caspase-8; RIP3: receptor-interacting protein 3; NF-kB: nuclear factor kappa.