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dc.contributor.authorLauritzen, Knut H.
dc.contributor.authorOlsen, Maria Belland
dc.contributor.authorAhmed, Mohammed Shakil
dc.contributor.authorYang, Kuan
dc.contributor.authorRinholm, Johanne Egge
dc.contributor.authorBergersen, Linda H.
dc.contributor.authorEsbensen, Qin Ying
dc.contributor.authorSverkeli, Lars Jansen
dc.contributor.authorZiegler, Mathias
dc.contributor.authorAttramadal, Håvard
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorAukrust, Pål
dc.contributor.authorYndestad, Arne
dc.date.accessioned2021-09-07T12:22:21Z
dc.date.available2021-09-07T12:22:21Z
dc.date.created2021-09-02T11:22:37Z
dc.date.issued2021
dc.identifier.issn2050-084X
dc.identifier.urihttps://hdl.handle.net/11250/2774038
dc.description.abstractPoly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD+) as energy source. Prolonged PARP activity can drain cellular NAD+ reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac dysfunction via reduced NAD+ levels and loss of mitochondrial function and communication. Using a transgenic model, we demonstrate that high levels of mice cardiomyocyte mtDNA damage cause a reduction in NAD+ levels due to extreme DNA repair activity, causing impaired activation of NAD+-dependent SIRT3. In addition, we show that myocardial mtDNA damage in combination with high dosages of nicotinamideriboside (NR) causes an inhibition of sirtuin activity due to accumulation of nicotinamide (NAM), in addition to irregular cardiac mitochondrial morphology. Consequently, high doses of NR should be used with caution, especially when cardiomyopathic symptoms are caused by mitochondrial dysfunction and instability of mtDNA.en_US
dc.language.isoengen_US
dc.publishereLife Sciences Publicationsen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleInstability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communicationen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 the authorsen_US
dc.source.articlenumbere59828en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.doi10.7554/ELIFE.59828
dc.identifier.cristin1930756
dc.source.journaleLIFEen_US
dc.identifier.citationeLIFE. 2021, 10, e59828.en_US
dc.source.volume10en_US


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal