细胞酸乙辅酶A是一种信号代谢物,用于控制细胞衰变
Yifan Zhang1,2, Xiao Shen1,2, Yuan Shen1,2
1Fudan University Shanghai Cancer Center & School of Basic Medical Sciences & Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; The Shanghai Key Laboratory of Medical Epigenetics; State Key Laboratory of Brain Function and Disorders, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Nature
|November 12, 2025
概括
禁食会降低细胞溶液中的乙CoA (AcCoA),并通过NLRX1触发 mitophagy. 乙补充剂可以扭转这种情况,揭示AcCoA是关键的代谢信号,将营养状况与细胞衰减联系起来.
科学领域:
- 细胞生物学
- 代谢调节
- 自食
背景情况:
- 乙-CoA (AcCoA) 是营养代谢和三碳酸循环的核心.
- 营养状况和禁食一样,动态调节了AcCoA水平和代谢途径.
- 线粒体的选择性降解 (mitophagy) 在细胞平衡中起作用.
研究的目的:
- 研究细胞溶液AcCoA在调节细胞衰变中的作用.
- 确定将AcCoA水平与线粒细胞衰变联系起来的分子机制.
- 探索针对AcCoA-mitophagy轴的治疗潜力.
主要方法:
- 短期禁食和药物抑制关键代谢酶 (ACLY,SLC25A1,ACSS2) 以减少细胞质AcCoA.
- 补充乙酸盐以抵消AcCoA的减少.
- NLRX1 (NOD类受体家族X1成员) 的遗传破坏.
- 在体外和体内实验来评估菌.
- 研究蛋白与蛋白相互作用的生物化学测定 (NLRX1-AcCoA).
主要成果:
- 由禁食或酶抑制引起的细胞质AcCoA水平降低会引发细胞衰老.
- 乙补充剂有效地抵消了由AcCoA减少引起的线粒.
- NLRX1对于减少细胞系AcCoA的反应中介的作用至关重要.
- NLRX1直接与细胞质AcCoA结合,调节其与LC3的构成和相互作用.
- 该AcCoA-NLRX1通路与KRAS抑制剂诱导的线粒细胞衰变和耐药性有关.
结论:
- 细胞 AcCoA 作为一个信号代谢物,通过它的受体 NLRX1 将营养代谢与细胞连接起来.
- 该AcCoA-NLRX1轴代表了一种促进KRAS抑制剂耐药性的新代谢机制.
- 针对这种途径可以为代谢疾病和癌症治疗提供治疗策略.
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