Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan
AbstractMitochondrial 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. View Full-Text
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Hirose, M.; Schilf, P.; Zarse, K.; Busch, H.; Fuellen, G.; Jöhren, O.; Köhling, R.; König, I.R.; Richer, B.; Rupp, J.; Schwaninger, M.; Seeger, K.; Sina, C.; Ristow, M.; Ibrahim, S.M. Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan. Genes 2019, 10, 532.
Hirose M, Schilf P, Zarse K, Busch H, Fuellen G, Jöhren O, Köhling R, König IR, Richer B, Rupp J, Schwaninger M, Seeger K, Sina C, Ristow M, Ibrahim SM. Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan. Genes. 2019; 10(7):532.Chicago/Turabian Style
Hirose, Misa; Schilf, Paul; Zarse, Kim; Busch, Hauke; Fuellen, Georg; Jöhren, Olaf; Köhling, Rüdiger; König, Inke R.; Richer, Barbara; Rupp, Jan; Schwaninger, Markus; Seeger, Karsten; Sina, Christian; Ristow, Michael; Ibrahim, Saleh M. 2019. "Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan." Genes 10, no. 7: 532.
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