NFκB和JNK通路在ESCRT-I缺陷时调解代谢适应
Jaroslaw Cendrowski1,2, Marta Wrobel3, Michal Mazur3
1Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland. jaroslaw.cendrowski@nio.gov.pl.
Cellular and molecular life sciences : CMLS
|November 19, 2024
概括
运输所需的内体组分复合体 (ESCRT) 功能障碍会损害 lysosomal 营养循环. 缺少ESCRT-I将细胞代谢重新编程为糖解,影响细胞营养利用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 代谢生物化学 代谢生物化学
背景情况:
- 运输所需的内体组分复合体 (ESCRT) 促进了溶酶体降解以进行营养回收.
- 在此之前,ESCRT功能障碍对细胞代谢的影响尚不清楚.
研究的目的:
- 研究ESCRT-I缺乏如何影响细胞代谢和基因表达.
- 阐明ESCRT缺陷细胞中代谢重编程背后的机制.
主要方法:
- 缺少TSG101或VPS28 (ESCRT-I组件) 的细胞的转录组分析.
- 分析代谢变化,包括基因表达,营养消耗和脂质积累.
- 研究信号通路 (NFκB,JNK) 和器官功能 (ER,线粒体).
主要成果:
- 缺少ESCRT-I降低了脂肪酸和氨基酸氧化基因的调节,同时提高了糖分分解酶的调节.
- 观察到类似于华堡效应的重编程:增加葡萄糖/谷氨的摄取,乳酸的产生和脂质的积累.
- 由于ESCRT-I的耗尽,ER扩张,线粒体积累,NFκB和JNK信号的激活.
结论:
- 缺少ESCRT-I会诱导新陈代谢对糖解的重编程,有利于细胞外营养素的使用,而不是溶解体营养素.
- 扰乱的溶酶体降解和激活的压力信号通路介导了这种代谢转变.
- 这项研究揭示了ESCRT在通过调节营养来源利用来维持新陈代谢平衡的关键作用.
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