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Hirose, M.* ; Schilf, P.* ; Gupta, Y.* ; Zarse, K.* ; Künstner, A.* ; Fähnrich, A.* ; Busch, H.* ; Yin, J.* ; Wright, M.N.* ; Ziegler, A.* ; Vallier, M.* ; Belheouane, M.* ; Baine, J.F.* ; Tautz, D.* ; Johann, K.* ; Oelkrug, R.* ; Mittag, J.* ; Lehnert, H.* ; Othmann, A.* ; Jöhren, O.* ; Schwaninger, M.* ; Prehn, C. ; Adamski, J. ; Shima, K.* ; Rupp, J.* ; Häsler, R.* ; Fuellen, G.* ; Köhling, R.* ; Ristow, M.* ; Ibrahim, S.M.*

Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice.

Sci. Rep. 8:5872 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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-mt) 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 5872 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Molekulare Endokrinologie und Metabolismus (MEM)