First Author | Hirose M | Year | 2019 |
Journal | Genes (Basel) | Volume | 10 |
Issue | 7 | PubMed ID | 31337008 |
Mgi Jnum | J:290761 | Mgi Id | MGI:6442699 |
Doi | 10.3390/genes10070532 | Citation | Hirose M, et al. (2019) Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan. Genes (Basel) 10(7) |
abstractText | 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. |