Necroptosis is a programmed form of necrotic cell death. Necrotic cell death has been considered a form of passive cell death. However, the discovery that TNFalpha mediated necrosis can be inhibited by a specific inhibitor of RIP1 kinase, necrostatin-1, led to the concept of necroptosis;. Necroptosis has now been established as a regulated necrotic cell death pathway controlled by RIP1 and RIP3 kinases.
Under conditions that are insufficient to trigger apoptosis, TNFα activates TNFR1 and in turn induces the recruitment of RIP1 kinase and other proteins to form complex I. Subsequently, these proteins dissociate from TNFR1 and RIP1 can be found in the cytosol in complex IIb, which includes RIP1, RIP3, caspase 8 and FADD. The formation of complex IIb leads to necroptosis.
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