Process of necroptosis

The process of necroptosis. The interaction between TNF and TNFR stimulates the assembly of the TNFR complex, which consists of TRADD, TRAF2, RIPK1, CIAP1/2, and LUBAC. This complex has the ability to facilitate the phosphorylation of RIPK1, which subsequently results in the phosphorylation of RIPK3. Ultimately, the activation of RIPK3 can also occur via the LPS-TLR signaling pathway in the presence of TRIF. The phosphorylation of RIPK3 is known to facilitate the phosphorylation of MLKL, which in turn can lead to its oligomerization and translocation to the cellular membrane. This event is responsible for the disruption of membrane integrity and cytosolic osmolarity, ultimately resulting in membrane permeabilization. Inhibition of NF-κB activity driven by complex I can result in the induction of apoptosis through the involvement of complex II, comprising TRADD, TRAF2, RIPK1, FADD, casepase8, and cFLIP, which cleaves RIPK1 to prevent necroptosis. Additionally, the activation of MLKL can stimulate the NLRP3-caspase1 inflammasome, leading to the release of IL-1β and IL-18.

Publication

Programmed Cell Death in Liver Fibrosis (2023) Ruoyu Gao, et al. J Inflamm Res. 2023;16(2):NA. Figure: F1. Homo sapiens

Disease mentions