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Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis
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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.date.accessioned | 2023-08-14T14:30:04Z | |
dc.date.available | 2023-08-14T14:30:04Z | |
dc.date.issued | 2021-08-10 | |
dc.identifier | 292295414 | |
dc.identifier | b36335eb-4cd7-4764-babf-ca2f664f1e87 | |
dc.identifier | 85112103090 | |
dc.identifier | 34376668 | |
dc.identifier.citation | Bodineau , C , Tomé , M , Courtois , S , Costa , A S H , Sciacovelli , M , Rousseau , B , Richard , E , Vacher , P , Parejo-Pérez , C , Bessede , E , Varon , C , Soubeyran , P , Frezza , C , Murdoch , P D S , Villar , V H & Durán , R V 2021 , ' Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis ' , Nature Communications , vol. 12 , 4814 . https://doi.org/10.1038/s41467-021-25079-4 | en |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | ORCID: /0000-0003-2837-5018/work/140361369 | |
dc.identifier.uri | https://hdl.handle.net/10023/28164 | |
dc.description | Funding: 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). | en |
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. | |
dc.format.extent | 13 | |
dc.format.extent | 3127158 | |
dc.language.iso | eng | |
dc.relation.ispartof | Nature Communications | en |
dc.subject | QH301 Biology | en |
dc.subject | Chemistry(all) | en |
dc.subject | Biochemistry, Genetics and Molecular Biology(all) | en |
dc.subject | General | en |
dc.subject | Physics and Astronomy(all) | en |
dc.subject | DAS | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject | MCC | en |
dc.subject.lcc | QH301 | en |
dc.title | Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.identifier.doi | 10.1038/s41467-021-25079-4 | |
dc.description.status | Peer reviewed | en |
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