Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan
dc.contributor.author
Hirose, Misa
dc.contributor.author
Schilf, Paul
dc.contributor.author
Zarse, Kim
dc.contributor.author
Busch, Hauke
dc.contributor.author
Fuellen, Georg
dc.contributor.author
Jöhren, Olaf
dc.contributor.author
Köhling, Rüdiger
dc.contributor.author
König, Inke R.
dc.contributor.author
Richer, Barbara
dc.contributor.author
Rupp, Jan
dc.contributor.author
Schwaninger, Markus
dc.contributor.author
Seeger, Karsten
dc.contributor.author
Sina, Christian
dc.contributor.author
Ristow, Michael
dc.contributor.author
Ibrahim, Saleh M.
dc.date.accessioned
2019-08-16T07:27:05Z
dc.date.available
2019-08-16T02:19:00Z
dc.date.available
2019-08-16T07:27:05Z
dc.date.issued
2019-07
dc.identifier.issn
2073-4425
dc.identifier.other
10.3390/genes10070532
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/358948
dc.identifier.doi
10.3929/ethz-b-000358948
dc.description.abstract
Mitochondrial complex I—the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery—has been proposed to contribute to a variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear (nDNA) and mitochondrial DNA (mtDNA). While some association studies of mtDNA encoded complex I genes and lifespan in humans have been reported, experimental evidence and the functional consequence of such variants is limited to studies using invertebrate models. Here, we present experimental evidence that a homoplasmic mutation in the mitochondrially encoded complex I gene mt-Nd2 modulates lifespan by altering cellular tryptophan levels and, consequently, ageing-related pathways in mice. A conplastic mouse strain carrying a mutation at m.4738C > A in mt-Nd2 lived slightly, but significantly, shorter than the controls did. The same mutation led to a higher susceptibility to glucose intolerance induced by high-fat diet feeding. These phenotypes were not observed in mice carrying a mutation in another mtDNA encoded complex I gene, mt-Nd5, suggesting the functional relevance of particular mutations in complex I to ageing and age-related diseases.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
MDPI
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Conplastic mouse strains
en_US
dc.subject
mitochondrially encoded complex I
en_US
dc.subject
mitochondrial DNA (mtDNA)
en_US
dc.subject
lifespan
en_US
dc.subject
mt-Nd2
en_US
dc.subject
healthspan
en_US
dc.subject
glucose metabolism
en_US
dc.subject
mice
en_US
dc.title
Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-07-13
ethz.journal.title
Genes
ethz.journal.volume
10
en_US
ethz.journal.issue
7
en_US
ethz.pages.start
532
en_US
ethz.size
14 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
Basel
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::03976 - Ristow, Michael (ehemalig) / Ristow, Michael (former)
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 (ehemalig) / Ristow, Michael (former)
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
2019-08-16T02:19:04Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-08-16T07:27:13Z
ethz.rosetta.lastUpdated
2024-02-02T08:43:25Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Maternally%20Inherited%20Differences%20within%20Mitochondrial%20Complex%20I%20Control%20Murine%20Healthspan&rft.jtitle=Genes&rft.date=2019-07&rft.volume=10&rft.issue=7&rft.spage=532&rft.issn=2073-4425&rft.au=Hirose,%20Misa&Schilf,%20Paul&Zarse,%20Kim&Busch,%20Hauke&Fuellen,%20Georg&rft.genre=article&rft_id=info:doi/10.3390/genes10070532&
Files in this item
Publication type
-
Journal Article [130417]