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dc.contributor.author
D'Hulst, Gommaar
dc.contributor.author
Soro-Arnaiz, Ines
dc.contributor.author
Masschelein, Evi
dc.contributor.author
Veys, Koen
dc.contributor.author
Fitzgerald, Gillian
dc.contributor.author
Smeuninx, Benoit
dc.contributor.author
Kim, Sunghoon
dc.contributor.author
Deldicque, Louise
dc.contributor.author
Blaauw, Bert
dc.contributor.author
Carmeliet, Peter
dc.contributor.author
Breen, Leigh
dc.contributor.author
Koivunen, Peppi
dc.contributor.author
Zhao, Shi-Min
dc.contributor.author
De Bock, Katrien
dc.date.accessioned
2020-01-21T13:58:37Z
dc.date.available
2020-01-21T13:58:37Z
dc.date.issued
2020
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/s41467-019-13889-6
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/392696
dc.identifier.doi
10.3929/ethz-b-000389601
dc.description.abstract
mTORC1 is an important regulator of muscle mass but how it is modulated by oxygen and nutrients is not completely understood. We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mice (PHD1KO) reduces muscle mass. PHD1KO muscles show impaired mTORC1 activation in response to leucine whereas mTORC1 activation by growth factors or eccentric contractions was preserved. The ability of PHD1 to promote mTORC1 activity is independent of its hydroxylation activity but is caused by decreased protein content of the leucyl tRNA synthetase (LRS) leucine sensor. Mechanistically, PHD1 interacts with and stabilizes LRS. This interaction is promoted during oxygen and amino acid depletion and protects LRS from degradation. Finally, elderly subjects have lower PHD1 levels and LRS activity in muscle from aged versus young human subjects. In conclusion, PHD1 ensures an optimal mTORC1 response to leucine after episodes of metabolic scarcity.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-01-10
ethz.journal.title
Nature Communications
ethz.journal.volume
11
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
174
en_US
ethz.size
15 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::09560 - De Bock, Katrien / De Bock, Katrien
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02535 - Institut für Bewegungswiss. und Sport / Institut of Human Movement Sc. and Sport::09560 - De Bock, Katrien / De Bock, Katrien
en_US
ethz.date.deposited
2020-01-13T09:23:44Z
ethz.source
FORM
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-01-21T13:58:47Z
ethz.rosetta.lastUpdated
2024-02-02T10:12:16Z
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/389601
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/391817
ethz.COinS
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