Control of endothelial quiescence by FOXO-regulated metabolites

Detalhes bibliográficos
Autor(a) principal: Andrade, Jorge
Data de Publicação: 2021
Outros Autores: Shi, Chenyue, Costa, Ana S. H., Choi, Jeongwoon, Kim, Jaeryung, Doddaballapur, Anuradha, Sugino, Toshiya, Ong, Yu Ting, Castro, Marco, Zimmermann, Barbara, Kaulich, Manuel, Guenther, Stefan, Wilhelm, Kerstin, Kubota, Yoshiaki, Braun, Thomas, Koh, Gou Young, Grosso, Ana Rita, Frezza, Christian, Potente, Michael
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/47394
Resumo: © 2021 Springer Nature Limited. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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spelling Control of endothelial quiescence by FOXO-regulated metabolites© 2021 Springer Nature Limited. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Endothelial cells (ECs) adapt their metabolism to enable the growth of new blood vessels, but little is known how ECs regulate metabolism to adopt a quiescent state. Here, we show that the metabolite S-2-hydroxyglutarate (S-2HG) plays a crucial role in the regulation of endothelial quiescence. We find that S-2HG is produced in ECs after activation of the transcription factor forkhead box O1 (FOXO1), where it limits cell cycle progression, metabolic activity and vascular expansion. FOXO1 stimulates S-2HG production by inhibiting the mitochondrial enzyme 2-oxoglutarate dehydrogenase. This inhibition relies on branched-chain amino acid catabolites such as 3-methyl-2-oxovalerate, which increase in ECs with activated FOXO1. Treatment of ECs with 3-methyl-2-oxovalerate elicits S-2HG production and suppresses proliferation, causing vascular rarefaction in mice. Our findings identify a metabolic programme that promotes the acquisition of a quiescent endothelial state and highlight the role of metabolites as signalling molecules in the endothelium.Research in the M.P. laboratory was supported by the Max Planck Society, the European Research Council (ERC) Consolidator Grant EMERGE (773047), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project-ID 75732319 – SFB 834, the Leducq Foundation, the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action (814316), the Excellence Cluster Cardio-Pulmonary Institute (EXC 2026, project ID 390649896), the DZHK (German Centre for Cardiovascular Research), the Stiftung Charité, and the European Molecular Biology Organization (EMBO) Young Investigator Programme. Work in the T.B. laboratory was supported by the DFG – Project-ID 268555672 – SFB 1213. Work in the C.F. laboratory was supported by the Medical Research Council (MRC_MC_UU_12022/6). This work was performed with assistance from the CSHL Mass Spectrometry Shared Resource, which is supported by the Cancer Center Support Grant 5P30CA045508.Springer NatureRepositório da Universidade de LisboaAndrade, JorgeShi, ChenyueCosta, Ana S. H.Choi, JeongwoonKim, JaeryungDoddaballapur, AnuradhaSugino, ToshiyaOng, Yu TingCastro, MarcoZimmermann, BarbaraKaulich, ManuelGuenther, StefanWilhelm, KerstinKubota, YoshiakiBraun, ThomasKoh, Gou YoungGrosso, Ana RitaFrezza, ChristianPotente, Michael2021-04-13T15:53:38Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47394engNat Cell Biol. 2021 Apr;23(4):413-4231465-739210.1038/s41556-021-00637-61476-4679info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-20T18:05:45Zoai:repositorio.ul.pt:10451/47394Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T18:05:45Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Control of endothelial quiescence by FOXO-regulated metabolites
title Control of endothelial quiescence by FOXO-regulated metabolites
spellingShingle Control of endothelial quiescence by FOXO-regulated metabolites
Andrade, Jorge
title_short Control of endothelial quiescence by FOXO-regulated metabolites
title_full Control of endothelial quiescence by FOXO-regulated metabolites
title_fullStr Control of endothelial quiescence by FOXO-regulated metabolites
title_full_unstemmed Control of endothelial quiescence by FOXO-regulated metabolites
title_sort Control of endothelial quiescence by FOXO-regulated metabolites
author Andrade, Jorge
author_facet Andrade, Jorge
Shi, Chenyue
Costa, Ana S. H.
Choi, Jeongwoon
Kim, Jaeryung
Doddaballapur, Anuradha
Sugino, Toshiya
Ong, Yu Ting
Castro, Marco
Zimmermann, Barbara
Kaulich, Manuel
Guenther, Stefan
Wilhelm, Kerstin
Kubota, Yoshiaki
Braun, Thomas
Koh, Gou Young
Grosso, Ana Rita
Frezza, Christian
Potente, Michael
author_role author
author2 Shi, Chenyue
Costa, Ana S. H.
Choi, Jeongwoon
Kim, Jaeryung
Doddaballapur, Anuradha
Sugino, Toshiya
Ong, Yu Ting
Castro, Marco
Zimmermann, Barbara
Kaulich, Manuel
Guenther, Stefan
Wilhelm, Kerstin
Kubota, Yoshiaki
Braun, Thomas
Koh, Gou Young
Grosso, Ana Rita
Frezza, Christian
Potente, Michael
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Andrade, Jorge
Shi, Chenyue
Costa, Ana S. H.
Choi, Jeongwoon
Kim, Jaeryung
Doddaballapur, Anuradha
Sugino, Toshiya
Ong, Yu Ting
Castro, Marco
Zimmermann, Barbara
Kaulich, Manuel
Guenther, Stefan
Wilhelm, Kerstin
Kubota, Yoshiaki
Braun, Thomas
Koh, Gou Young
Grosso, Ana Rita
Frezza, Christian
Potente, Michael
description © 2021 Springer Nature Limited. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2021
dc.date.none.fl_str_mv 2021-04-13T15:53:38Z
2021
2021-01-01T00:00:00Z
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/47394
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dc.language.iso.fl_str_mv eng
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dc.relation.none.fl_str_mv Nat Cell Biol. 2021 Apr;23(4):413-423
1465-7392
10.1038/s41556-021-00637-6
1476-4679
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