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Regulation of mTORC1 by amino acids in mammalian cells: A general picture of recent advances

Shizhe Zhang1, Xueyan Lin1, Qiuling Hou1

  • 1Key Laboratory of Ruminant Nutrition and Physiology, College of Animal Science and Technology, Shandong Agricultural University, No. 61, Daizong Street, Tai'an, Shandong, China.

Animal Nutrition (Zhongguo Xu Mu Shou Yi Xue Hui)
|November 5, 2021
PubMed

Insights

The mechanistic target of rapamycin complex 1 (mTORC1) integrates signals to control cell growth. Amino acids uniquely activate mTORC1 through a complex lysosomal, cytoplasmic, and Golgi sensing network.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Biochemistry

Background:

  • The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and proliferation.
  • mTORC1 integrates diverse signals including energy status, growth factors, and amino acids.
  • While energy and growth factor signaling converges on the TSC-Rheb axis, amino acid signaling utilizes a distinct pathway.

Purpose of the Study:

  • To elucidate the unique mechanism of amino acid signal transmission to mTORC1.
  • To present a comprehensive overview of recent advances in understanding amino acid sensing pathways.
  • To illustrate the complex network of amino acid signaling converging on mTORC1.

Main Methods:

  • Literature review and synthesis of recent findings on mTORC1 signaling.
  • Analysis of identified amino acid sensors and signal transmission pathways.
  • Conceptual modeling of the integrated amino acid signaling network.

Main Results:

  • Various amino acids are sensed by specific sensors located in lysosomes, cytoplasm, and the Golgi apparatus.
  • These distinct amino acid signals converge on mTORC1, modulating its activity.
  • The convergence forms a complex signaling network characterized by synergistic, antagonistic, and feedback mechanisms.

Conclusions:

  • Amino acid signaling represents a unique and intricate pathway for mTORC1 regulation.
  • Recent discoveries reveal a sophisticated network of sensors and pathways for diverse amino acids.
  • This network integrates signals from multiple cellular compartments to fine-tune mTORC1 activity, impacting cell growth and proliferation.
Keywords:
Amino acidsLeucineMammalSignaling pathwaymTORC1

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