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
  • [31] Relationship of mTORC1 and ferroptosis in tumors
    Liao, Huilin
    Wang, Yueqing
    Zou, Lili
    Fan, Yanmei
    Wang, Xinyue
    Tu, Xiancong
    Zhu, Qiaobai
    Wang, Jun
    Liu, Xiaowen
    Dong, Chuanjiang
    DISCOVER ONCOLOGY, 2024, 15 (01)
  • [32] Multistep regulation of TFEB by MTORC1
    Vega-Rubin-de-Celis, Silvia
    Pena-Llopis, Samuel
    Konda, Meghan
    Brugarolas, James
    AUTOPHAGY, 2017, 13 (03) : 464 - 472
  • [33] Suppression of Lysosome Function Induces Autophagy via a Feedback Down-regulation of MTOR Complex 1 (MTORC1) Activity
    Li, Min
    Khambu, Bilon
    Zhang, Hao
    Kang, Jeong-Han
    Chen, Xiaoyun
    Chen, Daohong
    Vollmer, Laura
    Liu, Pei-Qing
    Vogt, Andreas
    Yin, Xiao-Ming
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (50) : 35769 - 35780
  • [34] TRPML1 Promotes Protein Homeostasis in Melanoma Cells by Negatively Regulating MAPK and mTORC1 Signaling
    Kasitinon, Stacy Y.
    Eskiocak, Ugur
    Martin, Misty
    Bezwada, Divya
    Khivansara, Vishal
    Tasdogan, Alpaslan
    Zhao, Zhiyu
    Mathews, Thomas
    Aurora, Arin B.
    Morrison, Sean J.
    CELL REPORTS, 2019, 28 (09): : 2293 - +
  • [35] Regulation of Hematopoiesis and Methionine Homeostasis by mTORC1 Inhibitor NPRL2
    Dutchak, Paul A.
    Laxman, Sunil
    Estill, Sandi Jo
    Wang, Chensu
    Wang, Yun
    Wang, Yiguang
    Bulut, Gamze B.
    Gao, Jinming
    Huang, Lily J.
    Tu, Benjamin P.
    CELL REPORTS, 2015, 12 (03): : 371 - 379
  • [36] mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress
    Grahammer, Florian
    Haenisch, Nora
    Steinhardt, Frederic
    Sander, Lukas
    Roerden, Malte
    Arnold, Frederic
    Cordts, Tomke
    Wanner, Nicola
    Reichardt, Wilfried
    Kerjaschki, Dontscho
    Ruegg, Markus A.
    Hall, Michael N.
    Moulin, Pierre
    Busch, Hauke
    Boerries, Melanie
    Walz, Gerd
    Artunc, Ferruh
    Huber, Tobias B.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (27) : E2817 - E2826
  • [37] Cholesterol regulates insulin-induced mTORC1 signaling
    V. Navyasree, Kolaparamba
    Ramesh, Shikha T.
    Umasankar, Perunthottathu K.
    JOURNAL OF CELL SCIENCE, 2023, 136 (22)
  • [38] Lysosome as a Central Hub for Rewiring PH Homeostasis in Tumors
    Chen, Ran
    Jaattela, Marja
    Liu, Bin
    CANCERS, 2020, 12 (09) : 1 - 12
  • [39] TFEB, a novel mTORC1 effector implicated in lysosome biogenesis, endocytosis and autophagy
    Pena-Llopis, Samuel
    Brugarolas, James
    CELL CYCLE, 2011, 10 (23) : 3987 - 3988
  • [40] The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics
    Pan, Zhenrui
    Zhang, Hanxiao
    Dokudovskaya, Svetlana
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (13)