.png){kind=icon}
返回
Lysosomal positioning coordinates cellular nutrient responses
.png){kind=icon}
OA
AI
DOI：10.1038/ncb2204.png)
.png){kind=icon}
.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
mTOR (mammalian target of rapamycin) signalling and macroautophagy (henceforth autophagy) regulate numerous pathological and physiological processes, including cellular responses to altered nutrient levels. However, the mechanisms regulating mTOR and autophagy remain incompletely understood. Lysosomes are dynamic intracellular organelles(1,2) intimately involved both in the activation of mTOR complex 1 (mTORC1) signalling and in degrading autophagic substrates(3-8). Here we report that lysosomal positioning coordinates anabolic and catabolic responses with changes in nutrient availability by orchestrating early plasma-membrane signalling events, mTORC1 signalling and autophagy. Activation of mTORC1 by nutrients correlates with its presence on peripheral lysosomes that are physically close to the upstream signalling modules, whereas starvation causes perinuclear clustering of lysosomes, driven by changes in intracellular pH. Lysosomal positioning regulates mTORC1 signalling, which in turn influences autophagosome formation. Lysosome positioning also influences autophagosome-lysosome fusion rates, and thus controls autophagic flux by acting at both the initiation and termination stages of the process. Our findings provide a physiological role for the dynamic state of lysosomal positioning in cells as a coordinator of mTORC1 signalling with autophagic flux.
Keyword:
AGGREGATE-PRONE PROTEINS
DROSOPHILA-MELANOGASTER
HUNTINGTONS-DISEASE
NONNEURONAL CELLS
GENE-PRODUCTS
RAG GTPASES
AUTOPHAGY
MTOR
RAPAMYCIN
PATHWAY
AI总结
对已上传原文的论文进行重点信息的提取，主要内容包括：简要概述、研究摘要、背景介绍、关键亮点、图文解析、展望与总结。
期刊
IF:
19.1
论文数:
6.2K
被引数:
4.8W
机构
引用论文
High-Q Silicon Nitride Microresonator for Low Power Frequency Comb Initiation at Normal Dispersion Regime.png)
CLEO: 2015
CLEO: 2015IF0
PREAI
分享收藏Device Discovery and Context Registration in Static Context Header Compression NetworksInformationOAAI
InformationIF0
OAAI分享收藏A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycinOAAI
OAAI分享收藏Translational Approach of Using Ex Vivo Cytotoxicity and Early Clinical Data to Predict Teclistamab Efficacious Therapeutic Range in Multiple Myeloma Patients使用体外细胞毒性和早期临床数据预测多发性骨髓瘤患者Teclistamab有效治疗范围的翻译方法Blood
OAAI
BloodIF0
OAAI分享收藏Regulation of the mTOR Complex 1 Pathway by Nutrients, Growth Factors, and StressMOLECULAR CELLOAAI
MOLECULAR CELLIF16.6
OAAI分享收藏
查看更多内容