Figure 1.

Simplified version of necroptosis signal transduction events downstream of tumor necrosis factor-α/tumor necrosis factor receptor (TNFα/TNFR) interactions. Soluble TNFα binds TNFR and can trigger the formation of a pro-apoptotic (left, complex I) or pro-necroptotic (right, complex IIb) complex. In the absence of caspase-8 and presence of RIPK3, the pro-necroptotic complex IIb forms. After phosphorylation of RIPK1 and RIPK3, RIPK3 phosphorylates MLKL, which subsequently oligomerizes and is thought to insert into the cell membrane, forming pores. After cell membrane permeabilization, ion flux occurs, and intracellular contents are relapsed into the extracellular environment. Figure created with BioRender.com.