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通过在葡萄糖饥饿下增强 lysosomal 酸化,TCF25 作为营养传感器调节代谢适应和细胞死亡
Wenqing Ren1, Hui Jiang2, Qianqian Song2
1Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Cell reports
|August 22, 2025
概括
转录因子25 (TCF25) 通过控制 lysosomal 活动来调节营养应激期间的细胞死亡. 抑制TCF25可以防止细胞死亡和器官损伤,具有治疗潜力.
科学领域:
- 细胞生物学
- 代谢过程
- 分子生物学
背景情况:
- 细胞通过代谢途径的转变适应营养的限制.
- 长时间的营养压力可以诱导细胞死亡, 但调节机制仍然不清楚.
研究的目的:
- 确定葡萄糖饥饿引起的细胞死亡的关键调节者.
- 阐明转录因子25 (TCF25) 在细胞对营养应激反应中的作用.
主要方法:
- 全基因组CRISPR-Cas9查以确定遗传调节剂.
- 在葡萄糖饥饿下对溶解体通路基因丰富的分析.
- 研究TCF25在细胞代谢和细胞死亡中的功能.
主要成果:
- 一个查确定了参与葡萄糖饥饿的溶解体通路基因.
- 通过V-ATPase增强了TCF25的溶酶酸化和ATP生成.
- 长时间的饥饿会激活TCF25介导的费里丁,增加 lysosomal 膜的透性并导致细胞死亡.
- 通过 TCF25 或 V-ATPase 淘汰, 防止细胞死亡.
- 缺少TCF25可以保护小鼠免受肝缺血再输血损伤.
结论:
- TCF25作为一个关键的营养传感器,调节 lysosomal 功能.
- 在营养应激下,TCF25调节适应性反应 (自) 和细胞死亡 (费里丁).
- 抑制TCF25可能是代谢和缺血性疾病的治疗策略.
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