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线粒体VHL在低氧情况下重新连接细胞代谢

Guobang Li¹, Wenfeng Pan², Long Wu³

¹Department of Urology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, State Key Laboratory of Multi-organ Injury Prevention and Treatment, Southern Medical University, Guangzhou, China.

Cell metabolism

|December 23, 2025

概括

在慢性缺氧下,·希佩尔-林道 (VHL) 蛋白移动到线粒体,抑制白蛋白代谢. 这种代谢转变支持癌细胞生长,并与缺血性损伤有关.

科学领域:

细胞生物学细胞生物学
生物化学生物化学
代谢过程中的代谢.

背景情况:

·希佩尔-林道 (VHL) 蛋白通常向氧化HIF-α子单元,以降解在诺莫克西亚下,调节氧气传感.
在缺氧期间,当蛋白质氧化减少时,VHL蛋白的非正规作用仍然在很大程度上未被探索.

研究的目的:

为了研究VHL蛋白在慢性缺氧期间细胞代谢中的功能.
阐明VHL在HIF法规中的法定功能之外的非法定角色.

主要方法:

在慢性缺氧下对细胞质和线粒体VHL蛋白水平的定量分析.
生物化学测试以确定VHL和MCCC之间的相互作用2.
代谢流量分析,以评估氨酸代谢和谷氨酸溶解.
研究VHL酸化和MCCC2甲基化的调控作用.

主要成果:

慢性缺氧导致细胞质VHL的降解,剩余的蛋白质转移到线粒体.
线粒体VHL与MCCC2结合并抑制MCCC2,MCCC2是白代谢中的关键酶.
抑制白氨酸代谢导致白氨酸积累,激活谷氨酸脱酶并促进谷氨酸溶解.
这种新陈代谢重编程产生脂质和核酸,支持低毒细胞增殖.
通过SRC介导的VHL酸化和通过PRMT5介导的MCCC2甲基化调节VHL-MCCC2相互作用和代谢变化.

结论:

VHL蛋白质作为低氧代谢的线粒体调节器,与其在HIF降解中的正规作用不同.
在低氧条件下,VHL-MCCC2相互作用和随后的代谢重编程对于细胞存活和生长至关重要.
这些发现与了解缺血损伤和VHL在癌症发病过程中的作用有关.

关键词:

这是VHLVHL.缺氧缺氧是指缺氧的情况.氨酸 (leucine) 是一种蛋白质.代谢代谢代谢代谢线粒体中的线粒体.

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