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Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan

Authors :
Misa Hirose
Paul Schilf
Kim Zarse
Hauke Busch
Georg Fuellen
Olaf Jöhren
Rüdiger Köhling
Inke R. König
Barbara Richer
Jan Rupp
Markus Schwaninger
Karsten Seeger
Christian Sina
Michael Ristow
Saleh M. Ibrahim
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