Fig. 5.

Necroptosis is an example of antagonistic pleiotropy. Following viral infection, viral RNA (shown in red) transcribed by the host genome is sensed by ZBP1, which dimerizes with RIPK3 through its RHIM domain to activate RIPK3. Activated RIPK3 triggers necroptotic cell death through phosphorylation and membrane translocation of MLKL and this process of independent of RIPK1. Necroptosis is also induced by the age-related activation of pathways such as oxidative stress, mTOR signaling, and cell senescence, possibly through RIPK1-RIPK3-MLKL pathway. ZBP1: Z-DNA binding protein, also known as DAI or DLM-1; RHIM, RIP homotypic interaction motifs.