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/10362/124155
Resumo: (DFG, German Research Foundation) -Project-ID 75732319 -SFB 834, EXC 2026, project ID 390649896) DFG -Project-ID 268555672 -SFB 1213 MRC_MC_UU_12022/6 Cancer Center Support Grant 5P30CA045508
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oai_identifier_str oai:run.unl.pt:10362/124155
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Control of endothelial quiescence by FOXO-regulated metabolitesCell Biology(DFG, German Research Foundation) -Project-ID 75732319 -SFB 834, EXC 2026, project ID 390649896) DFG -Project-ID 268555672 -SFB 1213 MRC_MC_UU_12022/6 Cancer Center Support Grant 5P30CA045508Endothelial 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.UCIBIO - Applied Molecular Biosciences UnitDCV - Departamento de Ciências da VidaRUNAndrade, JorgeShi, ChenyueCosta, Ana S. H.Choi, JeongwoonKim, JaeryungDoddaballapur, AnuradhaSugino, ToshiyaOng, Yu TingCastro, MarcoZimmermann, BarbaraKaulich, ManuelGuenther, StefanWilhelm, KerstinKubota, YoshiakiBraun, ThomasKoh, Gou YoungGrosso, Ana RitaFrezza, ChristianPotente, Michael2021-09-08T00:20:19Z2021-042021-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://hdl.handle.net/10362/124155eng1465-7392PURE: 33591985https://doi.org/10.1038/s41556-021-00637-6info: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:RCAAP2024-05-22T17:55:53Zoai:run.unl.pt:10362/124155Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T17:55:53Repositório 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
Cell Biology
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 UCIBIO - Applied Molecular Biosciences Unit
DCV - Departamento de Ciências da Vida
RUN
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
dc.subject.por.fl_str_mv Cell Biology
topic Cell Biology
description (DFG, German Research Foundation) -Project-ID 75732319 -SFB 834, EXC 2026, project ID 390649896) DFG -Project-ID 268555672 -SFB 1213 MRC_MC_UU_12022/6 Cancer Center Support Grant 5P30CA045508
publishDate 2021
dc.date.none.fl_str_mv 2021-09-08T00:20:19Z
2021-04
2021-04-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/124155
url http://hdl.handle.net/10362/124155
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1465-7392
PURE: 33591985
https://doi.org/10.1038/s41556-021-00637-6
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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