Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis.

Bodineau, Clément, Tomé, Mercedes, Courtois, Sarah, Costa, Ana SH, Sciacovelli, Marco, Rousseau, Benoit, Richard, Elodie, Vacher, Pierre, Parejo-Pérez, Carlos, Bessede, Emilie, Varon, Christine, Soubeyran, Pierre, Frezza, Christian, Murdoch, Piedad Del Socorro, Villar, Victor H, Durán, Raúl V (August 2021) Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis. Nature Communications, 12 (1). p. 4814. ISSN 2041-1723

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Abstract

Glutamoptosis is the induction of apoptotic cell death as a consequence of the aberrant activation of glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role of the bioenergetic sensor AMPK during glutamoptosis is not defined yet. Here, we show that AMPK reactivation blocks both the glutamine-dependent activation of mTORC1 and glutamoptosis in vitro and in vivo. We also show that glutamine is used for asparagine synthesis and the GABA shunt to produce ATP and to inhibit AMPK, independently of glutaminolysis. Overall, our results indicate that glutamine metabolism is connected with mTORC1 activation through two parallel pathways: an acute alpha-ketoglutarate-dependent pathway; and a secondary ATP/AMPK-dependent pathway. This dual metabolic connection between glutamine and mTORC1 must be considered for the future design of therapeutic strategies to prevent cell growth in diseases such as cancer.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell proliferation organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes organism description > animal > gender bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > mTORC1 organism description > animal > gender > male organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Costa, Ana SH
Communities:	CSHL labs > Pappin lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	10 August 2021
Date Deposited:	18 Aug 2021 13:42
Last Modified:	23 Jan 2024 18:36
PMCID:	PMC8355106
URI:	https://repository.cshl.edu/id/eprint/40328

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