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

Mitochondrial - nuclear genetic interaction modulates whole body metabolism, adiposity and gene expression in vivo.
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DOI:
10.1016/j.ebiom.2018.08.036
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发表时间:
2018-10
期刊:
影响因子:
11.1
通讯作者:
Ballinger SW
Ballinger SW
中科院分区:
医学1区
文献类型:
--
作者:
Dunham-Snary KJ;Sandel MW;Sammy MJ;Westbrook DG;Xiao R;McMonigle RJ;Ratcliffe WF;Penn A;Young ME;Ballinger SW

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我们假设线粒体DNA(mtDNA)的变化会显着影响全身代谢,肥胖和基因表达对饮食的反应。因为在人类中直接测试这些预测是不可行的,我们使用了线粒体-核交换小鼠,它们在不同的小家鼠品系之间交换了核和线粒体基因组。结果表明,核-线粒体遗传背景组合显着改变代谢效率和身体组成。脂肪组织中的比较RNA测序分析也表明,在相同的核背景下,mtDNA对调节核基因表达有明显的影响(差异表达基因的数量变化高达10倍),这表明孟德尔遗传学和线粒体遗传学都不能单方面控制基因表达。另外的分析表明,核-线粒体基因组组合以迄今为止未描述的方式调节基因表达。这些发现为理解复杂的遗传疾病易感性提供了一个新的框架。线粒体-核基因组组合调节代谢和身体组成。线粒体-核基因组组合调控脂肪组织基因表达。线粒体-核基因组组合产生不同的基因表达谱。孟德尔遗传学和线粒体遗传学都不单方面控制基因表达。
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. Mitochondrial-nuclear genome combination modulates metabolism and body composition. Mitochondrial-nuclear genome combination regulates adipose tissue gene expression. Mitochondrial-nuclear genome combination creates distinct gene expression profiles. Mendelian nor mitochondrial genetics unilaterally control gene expression.
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