DC Field | Value | Language |
---|---|---|
dc.contributor.author | Andrade, Jorge | ko |
dc.contributor.author | Shi, Chenyue | ko |
dc.contributor.author | Costa, Ana S. H. | ko |
dc.contributor.author | Choi, Jeongwoon | ko |
dc.contributor.author | Kim, Jaeryung | ko |
dc.contributor.author | Doddaballapur, Anuradha | ko |
dc.contributor.author | Sugino, Toshiya | ko |
dc.contributor.author | Ong, Yu Ting | ko |
dc.contributor.author | Castro, Marco | ko |
dc.contributor.author | Zimmermann, Barbara | ko |
dc.contributor.author | Kaulich, Manuel | ko |
dc.contributor.author | Guenther, Stefan | ko |
dc.contributor.author | Wilhelm, Kerstin | ko |
dc.contributor.author | Kubota, Yoshiaki | ko |
dc.contributor.author | Braun, Thomas | ko |
dc.contributor.author | Koh, Gou Young | ko |
dc.contributor.author | Grosso, Ana Rita | ko |
dc.contributor.author | Frezza, Christian | ko |
dc.contributor.author | Potente, Michael | ko |
dc.date.accessioned | 2021-05-12T05:50:24Z | - |
dc.date.available | 2021-05-12T05:50:24Z | - |
dc.date.created | 2021-05-04 | - |
dc.date.created | 2021-05-04 | - |
dc.date.issued | 2021-04 | - |
dc.identifier.citation | NATURE CELL BIOLOGY, v.23, no.4, pp.413 - U210 | - |
dc.identifier.issn | 1465-7392 | - |
dc.identifier.uri | http://hdl.handle.net/10203/283672 | - |
dc.description.abstract | Andrade et al. show that FOXO1 regulates mitochondrial metabolism to stimulate the production of the metabolite S-2HG to promote acquisition of a quiescent endothelial state. 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. | - |
dc.language | English | - |
dc.publisher | NATURE RESEARCH | - |
dc.title | Control of endothelial quiescence by FOXO-regulated metabolites | - |
dc.type | Article | - |
dc.identifier.wosid | 000635868900003 | - |
dc.identifier.scopusid | 2-s2.0-85103558649 | - |
dc.type.rims | ART | - |
dc.citation.volume | 23 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 413 | - |
dc.citation.endingpage | U210 | - |
dc.citation.publicationname | NATURE CELL BIOLOGY | - |
dc.identifier.doi | 10.1038/s41556-021-00637-6 | - |
dc.contributor.localauthor | Koh, Gou Young | - |
dc.contributor.nonIdAuthor | Andrade, Jorge | - |
dc.contributor.nonIdAuthor | Shi, Chenyue | - |
dc.contributor.nonIdAuthor | Costa, Ana S. H. | - |
dc.contributor.nonIdAuthor | Kim, Jaeryung | - |
dc.contributor.nonIdAuthor | Doddaballapur, Anuradha | - |
dc.contributor.nonIdAuthor | Sugino, Toshiya | - |
dc.contributor.nonIdAuthor | Ong, Yu Ting | - |
dc.contributor.nonIdAuthor | Castro, Marco | - |
dc.contributor.nonIdAuthor | Zimmermann, Barbara | - |
dc.contributor.nonIdAuthor | Kaulich, Manuel | - |
dc.contributor.nonIdAuthor | Guenther, Stefan | - |
dc.contributor.nonIdAuthor | Wilhelm, Kerstin | - |
dc.contributor.nonIdAuthor | Kubota, Yoshiaki | - |
dc.contributor.nonIdAuthor | Braun, Thomas | - |
dc.contributor.nonIdAuthor | Grosso, Ana Rita | - |
dc.contributor.nonIdAuthor | Frezza, Christian | - |
dc.contributor.nonIdAuthor | Potente, Michael | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
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