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Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan
- Source :
- Genes, Vol 10, Iss 7, p 532 (2019)
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 20734425 and 10070532
- Volume :
- 10
- Issue :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0589b49b8a25435aab07f5330fbab6c3
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/genes10070532