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
相关论文
共 50 条
  • [1] Suppressing mTORC1 on the lysosome
    Raiborg, Camilla
    Schink, Kay O.
    Stenmark, Harald
    EMBO JOURNAL, 2017, 36 (13): : 1809 - 1810
  • [2] The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis
    Roczniak-Ferguson, Agnes
    Petit, Constance S.
    Froehlich, Florian
    Qian, Sharon
    Ky, Jennifer
    Angarola, Brittany
    Walther, Tobias C.
    Ferguson, Shawn M.
    SCIENCE SIGNALING, 2012, 5 (228)
  • [3] Spatial Control of the TSC Complex Integrates Insulin and Nutrient Regulation of mTORC1 at the Lysosome
    Menon, Suchithra
    Dibble, Christian C.
    Talbott, George
    Hoxhaj, Gerta
    Valvezan, Alexander J.
    Takahashi, Hidenori
    Cantley, Lewis C.
    Manning, Brendan D.
    CELL, 2014, 156 (04) : 771 - 785
  • [4] The role of mTORC1 on regulating tissue resident macrophage homeostasis
    Deng, W.
    Yang, J.
    Lin, X.
    Shin, J.
    Gao, J.
    Zhong, X. -P
    EUROPEAN JOURNAL OF IMMUNOLOGY, 2016, 46 : 856 - 856
  • [5] The Central Role of mTORC1 in Amino Acid Sensing
    Yue, Shusheng
    Li, Guanya
    He, Shanping
    Li, Tingting
    CANCER RESEARCH, 2022, 82 (17) : 2964 - 2974
  • [6] Lysosome positioning coordinates mTORC1 activity and autophagy
    Poues, Christian
    Codogno, Patrice
    NATURE CELL BIOLOGY, 2011, 13 (04) : 342 - 344
  • [7] The lysosome: a crucial hub for AMPK and mTORC1 signalling
    Carroll, Bernadette
    Dunlop, Elaine A.
    BIOCHEMICAL JOURNAL, 2017, 474 (09) : 1453 - 1466
  • [8] Non-canonical mTORC1 signaling at the lysosome
    Napolitano, Gennaro
    Di Malta, Chiara
    Ballabio, Andrea
    TRENDS IN CELL BIOLOGY, 2022, 32 (11) : 920 - 931
  • [9] Nutrient regulation of mTORC1 at a glance
    Condon, Kendall J.
    Sabatini, David M.
    JOURNAL OF CELL SCIENCE, 2019, 132 (21)
  • [10] Lysosome positioning coordinates mTORC1 activity and autophagy
    Christian Poüs
    Patrice Codogno
    Nature Cell Biology, 2011, 13 : 342 - 344