Control of endothelial quiescence by FOXO-regulated metabolites
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
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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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 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/47394 |
url |
http://hdl.handle.net/10451/47394 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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