Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion

Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as…

• NN
  National Natural Science Foundation of China

  Awards: 81722016, 82071191, 2018YFC1312300, 81801182
• SU
  Sichuan University

  Award: ZYYC20007
• WC
  West China Hospital, Sichuan University

  Awards: ZYYC20009, 1.3.5 project, 1.3.5, ZYYC20007, Z2021LC001