USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy

Ferroptosis is an iron-dependent type of regulated cell death resulting from extensive lipid peroxidation and plays a critical role in various physiological and pathological processes. However, the regulatory mechanisms for ferroptosis sensitivity remain incompletely understood. Here, we report that homozygous deletion of Usp8 (ubiquitin-specific protease 8) in intestinal epithelial cells (IECs) leads to architectural changes in the colonic epithelium and shortens mouse lifespan accompanied by increased IEC death and signs of lipid peroxidation. However, mice with heterozygous deletion of Usp8 in IECs display normal phenotype and become resistant to azoxymethane/dextran sodium sulfate–induced colorectal…

• NN
  National Natural Science Foundation of China

  Awards: 82103149, 82273062, 31970732
• CP
  China Postdoctoral Science Foundation

  Award: 2022M722462
• ZU
  Zhengzhou University
• WU
  Wuhan University
• ZH
  Zhongnan Hospital of Wuhan University