Bilirubin directly activates RIPK3 to induce non-classical necroptosis - PubMed
4 hours ago
- #bilirubin
- #necroptosis
- #neurotoxicity
- Bilirubin activates RIPK3 to induce non-classical necroptosis.
- Bilirubin binds to D161 and S102 residues in RIPK3's kinase domain, promoting oligomerization and autophosphorylation.
- This activation leads to MLKL activation, the primary effector of necroptosis.
- Bilirubin-induced necroptosis does not require the RHIM domain of RIPK3 or RHIM-containing proteins like ZBP1 and TRIF.
- Depletion of Ripk3 reduces bilirubin-induced neurotoxicity in mice.
- The study reveals a new mechanism of RIPK3-mediated necroptosis contributing to bilirubin neurotoxicity.