通过胆固醇出口在TM4SF5丰富的线粒体-溶解体接触点进行葡萄糖介导的线粒体重编程
Ji Eon Kim1,2, So-Young Park3, Chulhwan Kwak4
1Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Cancer communications (London, England)
|December 22, 2023
概括
跨膜4L六个家族成员5 (TM4SF5) 蛋白质转移到线粒体-溶解体接触点促进线粒体和胆固醇出口,影响葡萄糖代谢和肝癌的进展.
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
- 癌症研究 癌症研究
背景情况:
- 跨膜4L六个家族成员5 (TM4SF5) 蛋白质表现出亚细胞转位和代谢功能,但与细胞内贩运和代谢环境的联系仍然不清楚.
- 了解TM4SF5对内体细胞膜的动力学对于阐明其在代谢调节中的作用至关重要.
研究的目的:
- 为了研究TM4SF5定位在线粒体-溶解体接触点 (MLCS) 的代谢意义.
- 探索TM4SF5交通动态与代谢调节作用之间的相关性.
主要方法:
- 使用了体外细胞和体外动物模型.
- 采用了免疫光学,基于近距离标记的蛋白质组学和有机体复制技术.
- 研究了TM4SF5与FKBP8,NPC1和胆固醇的相互作用.
主要成果:
- 在FKBP8-TM4SF5相互作用的介导下,在葡萄糖补充时在MLCS中进行TM4SF5丰富.
- 富含TM4SF5的MLCS通过DRP1和线粒体受体促进线粒体分裂和线粒体受体.
- TM4SF5调解了溶酶体胆固醇向线粒体的输出,损害了氧化酸化,但保留了TCA循环和β氧化.
结论:
- 富含TM4SF5的MLCS通过胆固醇出口来调节葡萄糖代谢,从而进行线粒体重编程.
- 这一过程与肝细胞癌发生和肝细胞癌代谢有关.
- 线粒体重编程支持生物分子合成与癌症中的糖溶性能量一起.
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