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<p>An increasingly important factor in the development of acute respiratory distress syndrome (ARDS), a potentially fatal outcome of acute lung injury (ALI), is ferroptosis, a type of controlled cell death caused by excess iron and lipid peroxidation. To mimic the inflammatory response seen in sepsis, animal models of inflammation are often exposed to lipopolysaccharide (LPS) to induce ALI. The current research aims to examine how MIB2 (Mindbomb E3 ubiquitin ligase 2) interacts with ferroptosis by regulating GPX4, an important anti-ferroptotic protein, and how this contributes to the development of LPS-induced ALI. The results show that MIB2 expression is significantly increased in ALI models caused by LPS, and that inhibiting MIB2 in both in vivo and in vitro models reduces LPS-induced ferroptosis and boosts the inflammatory response. MIB2 was found to accelerate GPX4 degradation through a ubiquitination-dependent mechanism, leading to the initiation of ferroptosis during LPS-induced ALI. Furthermore, knocking down GPX4 was shown to reverse the protective effects of MIB2 knockdown on ferroptosis, emphasizing the critical role of MIB2-GPX4 regulation in ALI development. These findings shed light on the molecular processes of ferroptosis in ALI and suggest MIB2 as a potential therapeutic target for reducing or preventing LPS-induced lung damage.</p>

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MIB2 accelerates ferroptosis during lipopolysaccharide-induced acute lung injury through GPX4 degradation

  • 期刊论文

  • 发表日期：

    2026年1月10日

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  • Yanhong Kang,
  • Weiye Feng,
  • Lanlan Ning

摘要

An increasingly important factor in the development of acute respiratory distress syndrome (ARDS), a potentially fatal outcome of acute lung injury (ALI), is ferroptosis, a type of controlled cell death caused by excess iron and lipid peroxidation. To mimic the inflammatory response seen in sepsis, animal models of inflammation are often exposed to lipopolysaccharide (LPS) to induce ALI. The current research aims to examine how MIB2 (Mindbomb E3 ubiquitin ligase 2) interacts with ferroptosis by regulating GPX4, an important anti-ferroptotic protein, and how this contributes to the development of LPS-induced ALI. The results show that MIB2 expression is significantly increased in ALI models caused by LPS, and that inhibiting MIB2 in both in vivo and in vitro models reduces LPS-induced ferroptosis and boosts the inflammatory response. MIB2 was found to accelerate GPX4 degradation through a ubiquitination-dependent mechanism, leading to the initiation of ferroptosis during LPS-induced ALI. Furthermore, knocking down GPX4 was shown to reverse the protective effects of MIB2 knockdown on ferroptosis, emphasizing the critical role of MIB2-GPX4 regulation in ALI development. These findings shed light on the molecular processes of ferroptosis in ALI and suggest MIB2 as a potential therapeutic target for reducing or preventing LPS-induced lung damage.