dc.contributor.author	Bodineau, Clément
dc.contributor.author	Tomé, Mercedes
dc.contributor.author	Courtois, Sarah
dc.contributor.author	Costa, Ana S H.
dc.contributor.author	Sciacovelli, Marco
dc.contributor.author	Rousseau, Benoit
dc.contributor.author	Richard, Elodie
dc.contributor.author	Vacher, Pierre
dc.contributor.author	Parejo-Pérez, Carlos
dc.contributor.author	Bessede, Emilie
dc.contributor.author	Varon, Christine
dc.contributor.author	Soubeyran, Pierre
dc.contributor.author	Frezza, Christian
dc.contributor.author	Murdoch, Piedad Del Socorro
dc.contributor.author	Villar, Victor H.
dc.contributor.author	Durán, Raúl V.
dc.contributor.authoraffiliation	[Bodineau,C; Tomé,M; Murdoch,PDS; Durán,RV] Centro Andaluz de Biología Molecular y Medicina Regenerativa—CABIMER, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Universidad Pablo de Olavide, Seville, Spain. [Bodineau,C; Durán,RV] Institut Européen de Chimie et Biologie, INSERM, Université de Bordeaux, Pessac, France. [Courtois,S; Bessede,E; Varon,C] Bordeaux Research in Translational Oncology, INSERM, Université de Bordeaux, Bordeaux cedex, France. [Costa,ASH; Sciacovelli,M; Frezza,C] Medical Research Council Cancer Unit, Hutchison/ MRC Research Centre, Box, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK. [Costa,ASH] Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA. [Rousseau,B] Service Commun des Animaleries, Animalerie A2, University of Bordeaux, Bordeaux, France. [Richard,E; Vacher,P; Soubeyran,P; Durán,RV] INSERM, Institut Bergonié, Bordeaux, France. [Parejo-Pérez,C] Instituto de Bioquímica Vegetal y Fotosíntesis, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, Spain. [Murdoch,PDS] Departamento de Bioquímica Vegetal y Biología Molecular, Universidad de Sevilla, Seville, Spain. [Villar,VH] CRUK Beatson Institute, Glasgow, UK.
dc.contributor.funder	This work was supported by funds from the following institutions: Agencia Estatal de Investigación/European Regional Development Fund, European Union (PGC2018-096244-B-I00, SAF2016-75442-R), Ministry of Science, Innovation and Universities of Spain, Spanish National Research Council—CSIC, Institut National de la Santé et de la Recherche Médicale —INSERM, Université de Bordeaux, Fondation pour la Recherche Médicale, the Conseil Régional d’Aquitaine, SIRIC-BRIO, Fondation ARC, and Institut Européen de Chimie et Biologie. C.B. was recipient of fellowships from the Minister of Higher Education, Research and Innovation (France) and the Fondation ARC (France). We thank Prof. Patricia Boya (Centro de Investigaciones Biologicas, Madrid, Spain) for kindly providing with the ATG5+/+ and ATG5−/− MEFs. We thank Prof. Benoit Viollet (Institute Cochin, Paris, France) for kindly providing with the AMPK+/+ and AMPK−/− MEFs, and the CA-AMPK plasmid
dc.date.accessioned	2022-08-23T09:02:59Z
dc.date.available	2022-08-23T09:02:59Z
dc.date.issued	2021-08-10
dc.description.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.	es_ES
dc.description.version	Yes	es_ES
dc.identifier.citation	Bodineau C, Tomé M, Courtois S, Costa ASH, Sciacovelli M, Rousseau B, et al. Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis. Nat Commun. 2021 Aug 10;12(1):4814	es_ES
dc.identifier.doi	10.1038/s41467-021-25079-4	es_ES
dc.identifier.essn	2041-1723
dc.identifier.pmc	PMC8355106
dc.identifier.pmid	34376668	es_ES
dc.identifier.uri	http://hdl.handle.net/10668/3934
dc.journal.title	Nature Communications
dc.language.iso	en
dc.page.number	13 p.
dc.publisher	Springer Nature	es_ES
dc.relation.publisherversion	https://www.nature.com/articles/s41467-021-25079-4	es_ES
dc.rights	Atribución 4.0 Internacional	*
dc.rights.accessRights	Acceso abierto	es_ES
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	*
dc.subject	Asparagine	es_ES
dc.subject	Cell death	es_ES
dc.subject	Cells	es_ES
dc.subject	Glutamine	es_ES
dc.subject	Growth	es_ES
dc.subject	Rôle	es_ES
dc.subject	Signal transduction	es_ES
dc.subject	Asparagina	es_ES
dc.subject	Muerte celular	es_ES
dc.subject	Células	es_ES
dc.subject	Glutamina	es_ES
dc.subject	Crecimiento	es_ES
dc.subject	Rol	es_ES
dc.subject	Transducción de señales	es_ES
dc.subject.mesh	Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::AMP-Activated Protein Kinases	es_ES
dc.subject.mesh	Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleotides::Purine Nucleotides::Adenine Nucleotides::Adenosine Triphosphate	es_ES
dc.subject.mesh	Medical Subject Headings::Organisms::Eukaryota::Animals	es_ES
dc.subject.mesh	Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents	es_ES
dc.subject.mesh	Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis	es_ES
dc.subject.mesh	Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor	es_ES
dc.subject.mesh	Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation	es_ES
dc.subject.mesh	Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Basic::Glutamine	es_ES
dc.subject.mesh	Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::HCT116 Cells	es_ES
dc.subject.mesh	Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Transformed::HEK293 Cells	es_ES
dc.subject.mesh	Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred Strains::Mice, Inbred NOD	es_ES
dc.subject.mesh	Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Transgenic::Mice, Knockout	es_ES
dc.subject.mesh	Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, SCID	es_ES
dc.subject.mesh	Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Signal Transduction	es_ES
dc.title	Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis	es_ES
dc.type	research article
dc.type.hasVersion	VoR
dspace.entity.type	Publication

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