mTORC1 and Nutrient Homeostasis: The Central Role of the Lysosome

被引:127
|
作者
Rabanal-Ruiz, Yoana [1 ]
Korolchuk, Viktor I. [1 ]
机构
[1] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England
基金
英国生物技术与生命科学研究理事会;
关键词
mTOR; nutrient sensing; lysosome; growth; autophagy; AMINO-ACID TRANSPORTERS; NOVO PYRIMIDINE SYNTHESIS; TRANSFER-RNA SYNTHETASE; VACUOLAR H+-ATPASE; RAG GTPASES; TUMOR-SUPPRESSOR; KINASE-ACTIVITY; LEUCINE SENSOR; V-ATPASE; TRANSCRIPTION FACTORS;
D O I
10.3390/ijms19030818
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mechanistic target of rapamycin complex 1 (mTORC1) coordinates cellular growth and metabolism with environmental inputs to ensure that cells grow only under favourable conditions. When active, mTORC1 stimulates biosynthetic pathways including protein, lipid and nucleotide synthesis and inhibits cellular catabolism through repression of the autophagic pathway, thereby promoting cell growth and proliferation. The recruitment of mTORC1 to the lysosomal surface has been shown to be essential for its activation. This finding has significantly enhanced our knowledge of mTORC1 regulation and has focused the attention of the field on the lysosome as a signalling hub which coordinates several homeostatic pathways. The intriguing localisation of mTORC1 to the cellular organelle that plays a crucial role in catabolism enables mTORC1 to feedback to autophagy and lysosomal biogenesis, thus leading mTORC1 to enact precise spatial and temporal control of cell growth. This review will cover the signalling interactions which take place on the surface of lysosomes and the cross-talk which exists between mTORC1 activity and lysosomal function.
引用
收藏
页数:23
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