Fig. 1.

Necroptosis regulators and signaling pathways in necroptosis activation. Upon TNF receptor ligation, a signal transduction mediated via RIP1, caspase activation, and tBID cleavage occurs, resulting in apoptotic cell death. Active caspase-8 inhibits necroptosis via cleavage of RIP1 and RIP3. Inhibition of caspase leads to the formation of a physical complex of RIP1 with RIP3 to trigger downstream signaling events including MLKL and PGAM5 recruitment, and transduction of cytosolic death signals to mitochondria, resulting in necroptosis.