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<p>Hepatic ischemia‒reperfusion injury (HIRI) represents a frequently occurring pathological condition during liver surgery, yet the mechanisms governing HIRI remain inadequately comprehended. Here, we investigate the role of B-cell translocation gene 2 (Btg2) in HIRI. Btg2 is upregulated following HIRI. A 70% HIRI model using hepatocyte-specific <i>Btg2</i> transgenic and systemic <i>Btg2</i> knockout mice reveals that Btg2 deteriorates hepatic inflammation and apoptosis. In primary hepatocytes, Btg2 knockdown reduces hypoxia/reoxygenation (H/R)-induced inflammation and mitochondrial stress. Metabolomics indicates that taurine metabolism is significantly affected in the livers of <i>Btg2</i><sup>-/-</sup> mice. Mechanistically, Btg2 suppresses UFMylation of flavin-containing monooxygenase 1 (Fmo1), a key taurine synthesis enzyme, promoting its K48-linked ubiquitination and degradation. Virus-mediated <i>Fmo1</i> overexpression inhibits ferroptosis, apoptosis, and HIRI significantly both in vivo and in vitro. Virtual screening of natural compounds indicates that Daturataturin A (DTA) inhibits Btg2, thereby attenuating ferroptosis and HIRI. These results suggest that Btg2 may constitute a promising therapeutic target for HIRI.</p>

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Btg2 inhibits Fmo1 UFMylation thus exacerbating ferroptosis and apoptosis in hepatic ischemia-reperfusion injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Dadi Peng,
  • Yihua Wang,
  • Dengliang Lei,
  • Kezhen Zong,
  • Shanshan Li,
  • Yunhai Luo,
  • Qiuying Li,
  • Liqing Jiang,
  • Weifeng Huang,
  • Yulin Ou,
  • Huarong Yu,
  • Jiayin Yang,
  • Zuotian Huang,
  • Zhongjun Wu

摘要

Hepatic ischemia‒reperfusion injury (HIRI) represents a frequently occurring pathological condition during liver surgery, yet the mechanisms governing HIRI remain inadequately comprehended. Here, we investigate the role of B-cell translocation gene 2 (Btg2) in HIRI. Btg2 is upregulated following HIRI. A 70% HIRI model using hepatocyte-specific Btg2 transgenic and systemic Btg2 knockout mice reveals that Btg2 deteriorates hepatic inflammation and apoptosis. In primary hepatocytes, Btg2 knockdown reduces hypoxia/reoxygenation (H/R)-induced inflammation and mitochondrial stress. Metabolomics indicates that taurine metabolism is significantly affected in the livers of Btg2-/- mice. Mechanistically, Btg2 suppresses UFMylation of flavin-containing monooxygenase 1 (Fmo1), a key taurine synthesis enzyme, promoting its K48-linked ubiquitination and degradation. Virus-mediated Fmo1 overexpression inhibits ferroptosis, apoptosis, and HIRI significantly both in vivo and in vitro. Virtual screening of natural compounds indicates that Daturataturin A (DTA) inhibits Btg2, thereby attenuating ferroptosis and HIRI. These results suggest that Btg2 may constitute a promising therapeutic target for HIRI.