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Updated: Nov 20, 2025

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
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Methionine controls insulin/mammalian target of rapamycin complex 1 activity by modulating tuberous sclerosis complex

Seishu Gen1, Yu Matsumoto1, Tsukasa Suzuki1

  • 1Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.

Biochemical and Biophysical Research Communications
|January 22, 2021
PubMed

Insights

Methionine impacts tumor suppressor TSC2 stability and lysosomal localization. Insulin signaling promotes TSC2 degradation when methionine is scarce, revealing a crosstalk mechanism.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Oncology

Background:

  • Tuberous sclerosis complex 2 (TSC2) is a tumor suppressor protein regulating cell growth.
  • TSC2 activity is influenced by growth factors, energy, oxygen, and insulin.
  • Mammalian target of rapamycin complex 1 (mTORC1) activation, often linked to cancer, is inhibited by TSC2.

Purpose of the Study:

  • To investigate the impact of methionine on the insulin/TSC2/mTORC1 signaling pathway.
  • To elucidate the relationship between methionine availability and TSC2 protein regulation.
  • To understand the crosstalk between insulin signaling and methionine metabolism via TSC2.

Main Methods:

  • Cellular assays to assess TSC2 protein stability and localization.
  • Analysis of TSC2 protein levels under varying methionine conditions.
  • Investigation of insulin signaling activation and its effect on TSC2 degradation.
  • Lysosomal localization studies for TSC2.

Main Results:

  • Methionine was found to influence TSC2 protein stability.
  • Methionine deprivation led to the abolition of TSC2 localization to the lysosome.
  • Insulin signaling activation promoted TSC2 degradation, particularly under methionine-deprived conditions.
  • Evidence of crosstalk between insulin and methionine metabolism mediated by TSC2 was established.

Conclusions:

  • Methionine plays a critical role in regulating TSC2 stability and cellular localization.
  • Insulin signaling and methionine availability interact through TSC2, affecting cell growth pathways.
  • This crosstalk mechanism involving TSC2, insulin, and methionine offers potential therapeutic targets for TSC2-related disorders.
Keywords:
AKTAmino acidMammalian target of rapamycin complex 1MethionineS-adenosylmethionineTuberous sclerosis complex 2

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