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Updated: Sep 25, 2025

Study of Protein-protein Interactions in Autophagy Research
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Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

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Glutamine, MTOR and autophagy: a multiconnection relationship

Clément Bodineau1,2,3, Mercedes Tomé3, Piedad Del Socorro Murdoch3

  • 1Department of Genetics, Harvard Medical School, Boston, MA, USA.

Autophagy
|April 26, 2022
PubMed

Insights

Cancer cells utilize glutamine via glutaminolysis and the ASNS-GABA shunt to regulate the AMPK-MTORC1 axis. This reveals a metabolic network controlling cell growth and autophagy.

Area of Science:

  • Cellular metabolism
  • Molecular signaling pathways
  • Cancer cell biology

Background:

  • Cancer cells heavily rely on glutamine metabolism, primarily through glutaminolysis, to activate mechanistic target of rapamycin complex 1 (MTORC1).
  • The AMP-activated protein kinase (AMPK)-MTORC1 signaling axis is a critical regulator of cellular growth and proliferation.
  • Existing understanding primarily linked glutamine metabolism to AMPK activation via glutaminolysis.

Purpose of the Study:

  • To investigate the role of asparagine synthetase (ASNS) and the GABA shunt in the metabolic control of the AMPK-MTORC1 axis.
  • To elucidate the broader metabolic network connecting glutamine metabolism to MTORC1 signaling and autophagy.

Main Methods:

  • Analysis of glutamine metabolism pathways in cancer cells.
  • Investigating the function of ASNS and the GABA shunt in regulating AMPK-MTORC1 signaling.
  • Examining the interplay between glutaminolysis and the ASNS-GABA shunt in controlling autophagy.

Main Results:

  • Demonstrated that glutamine's influence on AMPK is not limited to glutaminolysis.
  • Identified ASNS and the GABA shunt as crucial for metabolic control of the AMPK-MTORC1 axis under glutamine sufficiency.
  • Elucidated a metabolic network where glutamine regulates MTORC1-macroautophagy/autophagy via two branches: glutaminolysis and the ASNS-GABA shunt.

Conclusions:

  • Glutamine metabolism influences cancer cell growth and proliferation through distinct pathways.
  • The ASNS-GABA shunt plays a significant role in regulating the AMPK-MTORC1 axis, independent of glutaminolysis.
  • Understanding this dual regulatory network offers new insights into targeting cancer metabolism.
Keywords:
ASNSGABA-shuntMTORC1glutamineglutamoptosis

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