Fig. 1.

Molecular switching from apoptosis to necroptosis. Once cells are stimulated with TNFα, FADD and caspase-8 dissociated from membrane form of TNF receptor reconstitutes a cytoplasmic complex and active caspase-8 within complex cleaves Bid that cause to transform Bax/Bak into multimers in mitochondria. Afterward, a series of downstream events result in default apoptotic death. In contrast, under the circumstances that apoptosis is blocked or hindered by chemical or biological factors, cells activate a back-up cell death programmed necrosis in an active and ordered fashion by a cascade of signaling pathway. In fact, RIP1 interacts physically with RIP3 to trigger consecutive downstream signaling events including MLKL and PGAM5 recruitments, which transmit cytosolic death signals to mitochondria.