RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells

Ferroptosis is a recently discovered form of programmed cell death, but its regulatory mechanisms remain poorly understood. Here, we show that the RNA-binding protein ZFP36/TTP (ZFP36 ring finger protein) plays a crucial role in regulating ferroptosis in hepatic stellate cells (HSCs). Upon exposure to ferroptosis-inducing compounds, the ubiquitin ligase FBXW7/CDC4 (F-box and WD repeat domain containing 7) decreased ZFP36 protein expression by recognizing SFSGLPS motif. FBXW7 plasmid contributed to classical ferroptotic events, whereas ZFP36 plasmid impaired FBXW7 plasmid-induced HSC ferroptosis. Interestingly, ZFP36 plasmid inhibited macroautophagy/autophagy activation by destabilizing ATG16L1 (autophagy…

• NN
  National Natural Science Foundation of China

  Awards: 31401210, 81270514, 81600483, and 31571455
• PA
  Priority Academic Program Development of Jiangsu Higher Education Institutions
• JK
  Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica

  Award: JKLPSE 201804