Scholarlink

<p>After damage from&#xa0;pathogenic, chemical or physical stress, endolysosomal membranes are repaired and resealed by the endosomal sorting complex required for transport (ESCRT) machinery, but how this membrane damage is sensed and translated into ESCRT recruitment is poorly understood. Here, we identify&#xa0;the two ATG8 E3-like ligases, ATG16L1 and TECPR1, as ion-dependent catalysts for ESCRT recruitment to damaged lysosomal membranes. Leakage from perforated lysosomes induces the proton sensitive V-ATPase-dependent recruitment of ATG16L1-ATG5-ATG12 complexes, or the calcium-sensitive sphingomyelin-dependent recruitment of TECPR1-ATG5-ATG12 complexes. In both cases, the E3-like complex-dependent ATG5-ATG12 conjugate is required for ESCRT recruitment to the damaged membrane, and stabilization of the ESCRT machinery. Collectively, this study establishes the ATG8 E3-like ligases as membrane damage sensors for ESCRT-mediated membrane repair.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The ATG8 E3-like ligases sense lysosomal damage and initiate ESCRT-mediated membrane repair

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月3日

查看全文
  • Dale P Corkery,
  • Deerada Wijayatunga,
  • Benedita K L Feron,
  • Laura K Herzog,
  • Anastasia Knyazeva,
  • Yao-Wen Wu

摘要

After damage from pathogenic, chemical or physical stress, endolysosomal membranes are repaired and resealed by the endosomal sorting complex required for transport (ESCRT) machinery, but how this membrane damage is sensed and translated into ESCRT recruitment is poorly understood. Here, we identify the two ATG8 E3-like ligases, ATG16L1 and TECPR1, as ion-dependent catalysts for ESCRT recruitment to damaged lysosomal membranes. Leakage from perforated lysosomes induces the proton sensitive V-ATPase-dependent recruitment of ATG16L1-ATG5-ATG12 complexes, or the calcium-sensitive sphingomyelin-dependent recruitment of TECPR1-ATG5-ATG12 complexes. In both cases, the E3-like complex-dependent ATG5-ATG12 conjugate is required for ESCRT recruitment to the damaged membrane, and stabilization of the ESCRT machinery. Collectively, this study establishes the ATG8 E3-like ligases as membrane damage sensors for ESCRT-mediated membrane repair.