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Substrate selectivity as a paradigm shift in mTORC1 signaling

Jiyoung Pan1, Stephanie A Fernandes2, Riko Hatakeyama3

  • 1Max Planck Institute for Biology of Ageing (MPI-AGE), 50931 Cologne, Germany.

Current Opinion in Cell Biology
|June 17, 2026
PubMed

Insights

The mechanistic target of rapamycin complex 1 (mTORC1) pathway is not a simple on/off switch but exhibits substrate specificity. Its activity and lysosomal localization can be uncoupled, allowing selective regulation of cellular processes.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Metabolism

Background:

  • The mechanistic target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth and metabolism.
  • It was traditionally considered a binary switch, promoting anabolism and inhibiting catabolism.

Purpose of the Study:

  • To review emerging evidence on the substrate specificity of mTORC1 signaling.
  • To discuss the functional uncoupling of mTORC1 activity and its lysosomal localization.
  • To explore the implications for understanding mTORC1 biology and human disease.

Main Methods:

  • Literature review of recent research on mTORC1 regulation and function.
  • Analysis of studies investigating substrate recruitment and subcellular localization.
  • Synthesis of findings on upstream regulatory pathways and post-translational modifications.

Main Results:

  • mTORC1 signaling is highly substrate-specific, not a simple binary switch.
  • mTORC1 activity and lysosomal localization can be functionally uncoupled.
  • This uncoupling allows selective phosphorylation of different target proteins.

Conclusions:

  • Emerging evidence refines the understanding of mTORC1 as a sophisticated regulator.
  • Substrate-specific regulation and functional uncoupling have significant implications for cell biology.
  • Dysregulation of these mechanisms may contribute to human health and disease.

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