RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome

Necroptosis is a type of programmed cell death with great significance in many pathological processes. Tumour necrosis factor-α(TNF), a proinflammatory cytokine, is a prototypic trigger of necroptosis. It is known that mitochondrial reactive oxygen species (ROS) promote necroptosis, and that kinase activity of receptor interacting protein 1 (RIP1) is required for TNF-induced necroptosis. However, how ROS function and what RIP1 phosphorylates to promote necroptosis are largely unknown. Here we show that three crucial cysteines in RIP1 are required for sensing ROS, and ROS subsequently activates RIP1 autophosphorylation on serine residue 161 (S161). The major function of RIP1 kinase activity in TNF-induced…

• NS
  National Science Foundation
• NN
  National Natural Science Foundation of China

  Awards: 2015CB553800, 31420103910, J1310027, 2014CB541804, 31330047, 91029304, B12001, 81630042
• HE
  Higher Education Discipline Innovation Project

  Award: B12001
• NK
  National Key Research and Development Program of China

  Awards: 2014CB541804, 2015CB553800, 2013CB944903, 91029304