Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan
König, Inke R.
Ibrahim, Saleh M.
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
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. Show more
Journal / seriesGenes
Pages / Article No.
SubjectConplastic mouse strains; mitochondrially encoded complex I; mitochondrial DNA (mtDNA); lifespan; mt-Nd2; healthspan; glucose metabolism; mice
156031 - Molekulare Charakterisierung neuer Spezies-unabhängiger Regulatoren systemischer Alterung (SNF)
MoreShow all metadata