Pichaud Nicolas, Bérubé Roxanne, Côté Geneviève, Belzile Claude, Dufresne France, Morrow Geneviève, Tanguay Robert M, Rand David M, Blier Pierre U
Laboratory of Comparative Biochemistry and Physiology, Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada.
Laboratoire de Physiologie Animale Intégrative, Département de Biologie, Université du Québec à Rimouski, Rimouski, QC, Canada.
Front Genet. 2019 Feb 20;10:130. doi: 10.3389/fgene.2019.00130. eCollection 2019.
Mitochondrial and nuclear genomes have to coevolve to ensure the proper functioning of the different mitochondrial complexes that are assembled from peptides encoded by both genomes. Mismatch between these genomes is believed to be strongly selected against due to the consequent impairments of mitochondrial functions and induction of oxidative stress. Here, we used a model harboring an incompatibility between a mitochondrial tRNA and its nuclear-encoded mitochondrial tyrosine synthetase to assess the cellular mechanisms affected by this incompatibility and to test the relative contribution of mitonuclear interactions and aging on the expression of impaired phenotypes. Our results show that the mitochondrial tRNA mutation caused a decrease in mitochondrial oxygen consumption in the incompatible nuclear background but no effect with the compatible nuclear background. Mitochondrial DNA copy number increased in the incompatible genotype but that increase failed to rescue mitochondrial functions. The flies harboring mismatch between nuclear and mitochondrial genomes had almost three times the relative mtDNA copy number and fifty percent higher rate of hydrogen peroxide production compared to other genome combinations at 25 days of age. We also found that aging exacerbated the mitochondrial dysfunctions. Our results reveal the tight interactions linking mitonuclear mismatch to mitochondrial dysfunction, mitochondrial DNA regulation, ROS production and aging.
线粒体基因组和核基因组必须共同进化，以确保由这两个基因组编码的肽组装而成的不同线粒体复合物能够正常发挥功能。由于线粒体功能受损和氧化应激的诱导，人们认为这两个基因组之间的不匹配会受到强烈的选择抑制。在这里，我们使用了一个模型，该模型中一个线粒体tRNA与其核编码的线粒体酪氨酸合成酶之间存在不相容性，以评估受这种不相容性影响的细胞机制，并测试线粒体-核相互作用和衰老对受损表型表达的相对贡献。我们的结果表明，线粒体tRNA突变在不相容的核背景中导致线粒体耗氧量减少，但在相容的核背景中没有影响。不相容基因型中线粒体DNA拷贝数增加，但这种增加未能挽救线粒体功能。与其他基因组组合相比，在25日龄时，核基因组和线粒体基因组不匹配的果蝇相对线粒体DNA拷贝数几乎高出三倍，过氧化氢产生率高出50%。我们还发现衰老加剧了线粒体功能障碍。我们的结果揭示了线粒体-核不匹配与线粒体功能障碍、线粒体DNA调控、活性氧产生和衰老之间的紧密联系。
