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dc.contributor.author
Hirose, Misa
dc.contributor.author
Schilf, Paul
dc.contributor.author
Gupta, Yask
dc.contributor.author
Zarse, Kim
dc.contributor.author
Kuenstner, Axel
dc.contributor.author
Fähnrich, Anke
dc.contributor.author
Busch, Hauke
dc.contributor.author
Yin, Junping
dc.contributor.author
Wright, Marvin N.
dc.contributor.author
Ziegler, Andreas
dc.contributor.author
Vallier, Marie
dc.contributor.author
Belheouane, Meriem
dc.contributor.author
Baines, John F.
dc.contributor.author
Tautz, Diethard
dc.contributor.author
Johann, Kornelia
dc.contributor.author
Oelkrug, Rebecca
dc.contributor.author
Mittag, Jens
dc.contributor.author
Lehnert, Hendrik
dc.contributor.author
Othman, Alaa
dc.contributor.author
Jöhren, Olaf
dc.contributor.author
Schwaninger, Markus
dc.contributor.author
Prehn, Cornelia
dc.contributor.author
Adamski, Jerzy
dc.contributor.author
Shima, Kensuke
dc.contributor.author
Rupp, Jan
dc.contributor.author
Häsler, Robert
dc.contributor.author
Fuellen, Georg
dc.contributor.author
Köhling, Rüdiger
dc.contributor.author
Ristow, Michael
dc.contributor.author
Ibrahim, Saleh M.
dc.date.accessioned
2018-06-21T16:26:00Z
dc.date.available
2018-01-15T17:25:22Z
dc.date.available
2018-04-24T15:57:21Z
dc.date.available
2018-06-21T16:26:00Z
dc.date.issued
2018
dc.identifier.issn
2045-2322
dc.identifier.other
10.1038/s41598-018-24290-6
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/229035
dc.identifier.doi
10.3929/ethz-b-000229035
dc.description.abstract
Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e., the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum of diseases but also physiological processes, including endurance exercise performance in athletes. However, the phenotypic consequences of limited levels of naturally arising heteroplasmy have not been experimentally studied to date. We hence generated a conplastic mouse strain carrying the mitochondrial genome of an AKR/J mouse strain (B6-mtAKR) in a C57BL/6 J nuclear genomic background, leading to >20% heteroplasmy in the origin of light-strand DNA replication (OriL). These conplastic mice demonstrate a shorter lifespan as well as dysregulation of multiple metabolic pathways, culminating in impaired glucose metabolism, compared to that of wild-type C57BL/6 J mice carrying lower levels of heteroplasmy. Our results indicate that physiologically relevant differences in mtDNA heteroplasmy levels at a single, functionally important site impair the metabolic health and lifespan in mice.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2018-04-12
ethz.journal.title
Scientific Reports
ethz.journal.volume
8
en_US
ethz.journal.abbreviated
Sci Rep
ethz.pages.start
5872
en_US
ethz.size
15 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Molekulare Charakterisierung neuer Spezies-unabhängiger Regulatoren systemischer Alterung
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
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::02540 - Institut für Translationale Medizin / Institute of Translational Medicine
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
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::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::03976 - Ristow, Michael / Ristow, Michael
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::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::03976 - Ristow, Michael / Ristow, Michael
ethz.grant.agreementno
156031
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projektförderung in Biologie und Medizin (Abteilung III)
ethz.date.deposited
2018-01-15T17:25:23Z
ethz.source
BATCH
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-06-21T16:26:17Z
ethz.rosetta.lastUpdated
2021-02-15T00:26:58Z
ethz.rosetta.versionExported
true
ethz.COinS
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