Glutaminolysis and autophagy in cancer

Autophagy. 2015;11(8):1198-208. doi: 10.1080/15548627.2015.1053680.


The remarkable metabolic differences between cancer cells and normal cells result in the potential for targeted cancer therapy. The upregulation of glutaminolysis provides energetic advantages to cancer cells. The recently described link between glutaminolysis and autophagy, mediated by MTORC1, may constitute an attractive target for therapeutic strategies. A combination of therapies targeting simultane-ously cell signaling, cancer metabolism, and autophagy can solve therapy resistance and tumor relapse problems, commonly observed in patients treated with most of the current targeted therapies. In this review we summarize the mechanistic link between glutaminolysis and autophagy, and discuss the impacts of these processes on cancer progression and the potential for therapeutic intervention.

Keywords: MTOR; ROS; autophagy; cancer; glutaminolysis; prolyl hydroxylases; α-ketoglutarate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy*
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic*
  • Glutamine / metabolism*
  • Humans
  • Ketoglutaric Acids / chemistry
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism
  • Neoplasm Recurrence, Local
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism


  • Ketoglutaric Acids
  • Multiprotein Complexes
  • Reactive Oxygen Species
  • Glutamine
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases