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Mitochondrial - nuclear genetic interaction modulates whole body metabolism, adiposity and gene expression in vivo.

Citation
Dunham-Snary, K. J., et al. “Mitochondrial - Nuclear Genetic Interaction Modulates Whole Body Metabolism, Adiposity And Gene Expression In Vivo.”. Ebiomedicine, pp. 316-328.
Center University of Alabama at Birmingham
Author Kimberly J Dunham-Snary, Michael W Sandel, Melissa J Sammy, David G Westbrook, Rui Xiao, Ryan J McMonigle, William F Ratcliffe, Arthur Penn, Martin E Young, Scott W Ballinger
Keywords adipose, gene expression, Metabolism, mitochondrial DNA, Mitochondrial gene therapy, Mitochondrial – nuclear exchange, Nuclear–mitochondrial interaction, obesity
Abstract

We hypothesized that changes in the mitochondrial DNA (mtDNA) would significantly influence whole body metabolism, adiposity and gene expression in response to diet. Because it is not feasible to directly test these predictions in humans we used Mitochondrial-Nuclear eXchange mice, which have reciprocally exchanged nuclear and mitochondrial genomes between different Mus musculus strains. Results demonstrate that nuclear-mitochondrial genetic background combination significantly alters metabolic efficiency and body composition. Comparative RNA sequencing analysis in adipose tissues also showed a clear influence of the mtDNA on regulating nuclear gene expression on the same nuclear background (up to a 10-fold change in the number of differentially expressed genes), revealing that neither Mendelian nor mitochondrial genetics unilaterally control gene expression. Additional analyses indicate that nuclear-mitochondrial genome combination modulates gene expression in a manner heretofore not described. These findings provide a new framework for understanding complex genetic disease susceptibility.

Year of Publication
2018
Journal
EBioMedicine
Volume
36
Number of Pages
316-328
Date Published
10/2018
ISSN Number
2352-3964
DOI
10.1016/j.ebiom.2018.08.036
Alternate Journal
EBioMedicine
PMID
30232024
PMCID
PMC6197375
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