Scholarlink

<p>Most membrane-bound organelles have been linked to the initiation and execution of ferroptosis. However, the role of the Golgi apparatus and its resident proteins in ferroptosis remain elusive. Here we show that ferroptosis inducer triggers rapid oxidation of Golgi membrane lipids in the early phase of ferroptosis, resulting in disruption of Golgi pH. The Golgi-localized transmembrane protein TMEM87A is identified to mediate ferroptosis resistance through buffering Golgi pH. Depletion of TMEM87A leads to Golgi overacidification, which impairs FSP1-mediated reduction of coenzyme Q. In vivo, TMEM87A ablation suppresses the progression of multiple murine tumors including melanoma, colorectal cancer and liver cancer. TMEM87A ablation also enhances antitumor T cell responses and potentiates PD1 blockade therapy. Clinically, tumoral TMEM87A expression negatively correlates with immunotherapy response and treatment outcome. Our study reveals that TMEM87A functions as a suppressor of tumoral ferroptosis by maintaining Golgi pH homeostasis and targeting TMEM87A is potent to augment cancer immunotherapy.</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

TMEM87A suppresses ferroptosis and increases cancer immunotherapy resistance by maintaining the Golgi apparatus pH homeostasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月21日

查看全文
  • Jing Li,
  • Yuhan Zhou,
  • Xiong Li,
  • Songlin Yin,
  • Yuan Gao,
  • Haotian Shang,
  • Yongfeng Lai,
  • Liguo Yang,
  • Ying Xue,
  • Xiaoxiao Li,
  • Yan Li,
  • Zhenzhen Chang,
  • Jing Chen,
  • Xiang Cheng,
  • Xiaoyan Zhang,
  • Qian Chu,
  • Fujia Lu,
  • Weimin Wang

摘要

Most membrane-bound organelles have been linked to the initiation and execution of ferroptosis. However, the role of the Golgi apparatus and its resident proteins in ferroptosis remain elusive. Here we show that ferroptosis inducer triggers rapid oxidation of Golgi membrane lipids in the early phase of ferroptosis, resulting in disruption of Golgi pH. The Golgi-localized transmembrane protein TMEM87A is identified to mediate ferroptosis resistance through buffering Golgi pH. Depletion of TMEM87A leads to Golgi overacidification, which impairs FSP1-mediated reduction of coenzyme Q. In vivo, TMEM87A ablation suppresses the progression of multiple murine tumors including melanoma, colorectal cancer and liver cancer. TMEM87A ablation also enhances antitumor T cell responses and potentiates PD1 blockade therapy. Clinically, tumoral TMEM87A expression negatively correlates with immunotherapy response and treatment outcome. Our study reveals that TMEM87A functions as a suppressor of tumoral ferroptosis by maintaining Golgi pH homeostasis and targeting TMEM87A is potent to augment cancer immunotherapy.