Scholarlink

<p>Efficient fatty acid (FA) re-esterification is essential for lipid homeostasis in adipocytes, yet the mechanisms coordinating Coenzyme A (CoA) availability at the endoplasmic reticulum (ER)—a major site of lipid synthesis—remain unclear. Here, we identify TMEM120A as an ER-resident CoA-binding protein that regulates intracellular FA metabolism. TMEM120A interacts with the ER-localized acyl-CoA synthetase ACSL1 and ACSL3 to promote long-chain acyl-CoA synthesis and channeling into the ER, thereby facilitating FA re-esterification and lipid cycling during lipolysis. By relieving acyl-CoA-mediated feedback inhibition of lipolysis, TMEM120A enhances lipid turnover while protecting against ER stress and lipotoxicity. Adipocyte-specific deletion of <i>Tmem120a</i> in mice impairs lipolysis-induced energy expenditure and exacerbates inflammation and metabolic dysfunction under high-fat diet conditions. These findings establish TMEM120A as a critical regulator of ER CoA handling and lipid flux, revealing a previously unrecognized mechanism that links intracellular CoA dynamics to systemic energy balance and metabolic health.</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

TMEM120A maintains adipose tissue lipid homeostasis through ER CoA channeling

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月21日

查看全文
  • Yoon Keun Cho,
  • Junhyuck Lee,
  • Yujin L. Jeong,
  • Minki Shim,
  • Xuan Linh Mai,
  • Chang Seomoon,
  • Cheol Woon Jung,
  • Yoon Ha Choi,
  • Sik Namgoong,
  • Young-Suk Jung,
  • Sung Won Kwon,
  • Juyong Lee,
  • Je Kyung Seong,
  • Sunghyouk Park,
  • Emilio P. Mottillo,
  • James G. Granneman,
  • Dong-Kyu Lee,
  • Jong Kyoung Kim,
  • Yun-Hee Lee

摘要

Efficient fatty acid (FA) re-esterification is essential for lipid homeostasis in adipocytes, yet the mechanisms coordinating Coenzyme A (CoA) availability at the endoplasmic reticulum (ER)—a major site of lipid synthesis—remain unclear. Here, we identify TMEM120A as an ER-resident CoA-binding protein that regulates intracellular FA metabolism. TMEM120A interacts with the ER-localized acyl-CoA synthetase ACSL1 and ACSL3 to promote long-chain acyl-CoA synthesis and channeling into the ER, thereby facilitating FA re-esterification and lipid cycling during lipolysis. By relieving acyl-CoA-mediated feedback inhibition of lipolysis, TMEM120A enhances lipid turnover while protecting against ER stress and lipotoxicity. Adipocyte-specific deletion of Tmem120a in mice impairs lipolysis-induced energy expenditure and exacerbates inflammation and metabolic dysfunction under high-fat diet conditions. These findings establish TMEM120A as a critical regulator of ER CoA handling and lipid flux, revealing a previously unrecognized mechanism that links intracellular CoA dynamics to systemic energy balance and metabolic health.