Title |
Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice
|
---|---|
Published in |
Scientific Reports, April 2018
|
DOI | 10.1038/s41598-018-24290-6 |
Pubmed ID | |
Authors |
Misa Hirose, Paul Schilf, Yask Gupta, Kim Zarse, Axel Künstner, Anke Fähnrich, Hauke Busch, Junping Yin, Marvin N. Wright, Andreas Ziegler, Marie Vallier, Meriem Belheouane, John F Baines, Diethard Tautz, Kornelia Johann, Rebecca Oelkrug, Jens Mittag, Hendrik Lehnert, Alaa Othman, Olaf Jöhren, Markus Schwaninger, Cornelia Prehn, Jerzy Adamski, Kensuke Shima, Jan Rupp, Robert Häsler, Georg Fuellen, Rüdiger Köhling, Michael Ristow, Saleh M. Ibrahim |
Abstract |
Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e., the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum of diseases but also physiological processes, including endurance exercise performance in athletes. However, the phenotypic consequences of limited levels of naturally arising heteroplasmy have not been experimentally studied to date. We hence generated a conplastic mouse strain carrying the mitochondrial genome of an AKR/J mouse strain (B6-mtAKR) in a C57BL/6 J nuclear genomic background, leading to >20% heteroplasmy in the origin of light-strand DNA replication (OriL). These conplastic mice demonstrate a shorter lifespan as well as dysregulation of multiple metabolic pathways, culminating in impaired glucose metabolism, compared to that of wild-type C57BL/6 J mice carrying lower levels of heteroplasmy. Our results indicate that physiologically relevant differences in mtDNA heteroplasmy levels at a single, functionally important site impair the metabolic health and lifespan in mice. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 30% |
Australia | 2 | 10% |
United Kingdom | 2 | 10% |
Germany | 1 | 5% |
Canada | 1 | 5% |
Italy | 1 | 5% |
Spain | 1 | 5% |
Unknown | 6 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 12 | 60% |
Scientists | 7 | 35% |
Practitioners (doctors, other healthcare professionals) | 1 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 77 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 17 | 22% |
Student > Ph. D. Student | 17 | 22% |
Student > Bachelor | 8 | 10% |
Student > Doctoral Student | 6 | 8% |
Student > Master | 6 | 8% |
Other | 7 | 9% |
Unknown | 16 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 25 | 32% |
Agricultural and Biological Sciences | 11 | 14% |
Neuroscience | 6 | 8% |
Medicine and Dentistry | 4 | 5% |
Immunology and Microbiology | 3 | 4% |
Other | 9 | 12% |
Unknown | 19 | 25% |