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Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation

Author

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  • Hayden Weng Siong Tan

    (National University of Singapore)

  • Arthur Yi Loong Sim

    (National University of Singapore)

  • Yun Chau Long

    (National University of Singapore)

Abstract

Activation of autophagy and elevation of glutamine synthesis represent key adaptations to maintain amino acid balance during starvation. In this study, we investigate the role of autophagy and glutamine on the regulation of mTORC1, a critical kinase that regulates cell growth and proliferation. We report that supplementation of glutamine alone is sufficient to restore mTORC1 activity during prolonged amino acid starvation. Inhibition of autophagy abolishes the restorative effect of glutamine, suggesting that reactivation of mTORC1 is autophagy-dependent. Inhibition of glutaminolysis or transamination impairs glutamine-mediated mTORC1 reactivation, suggesting glutamine reactivates mTORC1 specifically through its conversion to glutamate and restoration of non-essential amino acid pool. Despite a persistent drop in essential amino acid pool during amino acid starvation, crosstalk between glutamine and autophagy is sufficient to restore insulin sensitivity of mTORC1. Thus, glutamine metabolism and autophagy constitute a specific metabolic program which restores mTORC1 activity during amino acid starvation.

Suggested Citation

  • Hayden Weng Siong Tan & Arthur Yi Loong Sim & Yun Chau Long, 2017. "Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00369-y
    DOI: 10.1038/s41467-017-00369-y
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    Cited by:

    1. Clément Adam & Léa Paolini & Naïg Gueguen & Guillaume Mabilleau & Laurence Preisser & Simon Blanchard & Pascale Pignon & Florence Manero & Morgane Mao & Alain Morel & Pascal Reynier & Céline Beauvilla, 2021. "Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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