TMEM120A通过ER CoA道化维持脂肪组织脂质稳态
Yoon Keun Cho1, Junhyuck Lee1, Yujin L Jeong2
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Nature communications
|December 21, 2025
概括
TMEM120A 是一种 ER 蛋白质,它与辅酶 A (CoA) 结合,这对于脂肪酸 (FA) 代谢至关重要. 它增强了FA的再化,促进了脂质循环,并防止了代谢功能障碍.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
- 脂质代谢 脂质代谢是什么
背景情况:
- 有效的脂肪酸再化对于脂肪细胞脂质稳定至关重要.
- 协调辅酶A (CoA) 在内分泌网膜 (ER) 中用于脂质合成的可用性机制尚未完全理解.
研究的目的:
- 为了确定调节细胞内CoA可用性的蛋白质在ER.
- 阐明TMEM120A在脂肪酸代谢和脂质平衡中的作用.
主要方法:
- 鉴定TMEM120A作为一种ER-居住的CoA结合蛋白.
- 研究TMEM120A与乙-CoA合成酶 (ACSL1和ACSL3) 的相互作用.
- 使用小鼠模型分析TMEM120A在脂肪细胞脂解和脂质循环中的作用 (脂肪细胞特异性Tmem120a删除).
主要成果:
- TMEM120A促进长链乙-CoA的合成和道进入ER.
- TMEM120A通过缓解脂解的反抑制,促进脂肪酸再化并增强脂质循环.
- 在小鼠中,脂肪细胞特异性的Tmem120a删除会损害能量消耗,并在高脂肪饮食下加剧代谢功能障碍.
结论:
- TMEM120A是ER CoA处理和细胞内脂质流量的关键调节者.
- TMEM120A将细胞内CoA动态与系统能量平衡和代谢健康联系起来.
- TMEM120A通过调节脂质循环,防止ER压力和脂毒性.
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