Experimental Mitochondrial Genetics Group, School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, SA 5000, Australia.
Biomolecules. 2024 Nov 20;14(11):1477. doi: 10.3390/biom14111477.
Mitochondrial DNA (mtDNA) supplementation can rescue poor oocyte quality and overcome embryonic arrest. Here, we investigated a series of sexually mature pigs generated through autologous and heterologous mtDNA supplementation. Brain, liver and heart tissues underwent metabolite profiling using gas chromatography-mass spectrometry and gene expression analysis through RNA-seq. They were then assessed for mRNA-metabolite interactions. The comparison between overall mtDNA supplemented and control pigs revealed that mtDNA supplementation reduced the lipids stearic acid and elaidic acid in heart tissue. However, heterologous mtDNA supplemented-derived pigs exhibited lower levels of abundance of metabolites when compared with autologous-derived pigs. In the brain, these included mannose, mannose 6-phosphate and fructose 6-phosphate. In the liver, maltose and cellobiose, and in the heart, glycine and glutamate were affected. mRNA-metabolite pathway analysis revealed a correlation between malate and , , and in the liver and glutamate and , , and in the heart. Our outcomes demonstrate that mtDNA supplementation, especially heterologous supplementation, alters the metabolite and transcriptome profiles of brain, liver, and heart tissues. This is likely due to the extensive resetting of the balance between the nuclear and mitochondrial genomes in the preimplantation embryo, which induces a series of downstream effects.
线粒体 DNA（mtDNA）补充可以挽救卵母细胞质量差和胚胎停滞的问题。在这里，我们研究了一系列通过自体和异体 mtDNA 补充产生的性成熟猪。使用气相色谱-质谱法对脑、肝和心脏组织进行代谢物谱分析，并通过 RNA-seq 进行基因表达分析。然后评估它们的 mRNA-代谢物相互作用。与总体 mtDNA 补充猪相比，补充 mtDNA 的猪的心脏组织中 stearic acid 和 elaidic acid 等脂质减少。然而，与自体衍生的猪相比，异体 mtDNA 补充衍生的猪的代谢物丰度水平较低。在大脑中，包括甘露糖、甘露糖 6-磷酸和果糖 6-磷酸；在肝脏中，包括麦芽糖和纤维二糖；在心脏中，包括甘氨酸和谷氨酸。mRNA-代谢物途径分析显示，肝脏中 malate 与 、 、 和 ，以及心脏中 glutamate 与 、 、 和 之间存在相关性。我们的研究结果表明，mtDNA 补充，特别是异体补充，改变了脑、肝和心脏组织的代谢物和转录组图谱。这可能是由于前胚胎期核基因组和线粒体基因组之间的平衡广泛重置，从而引发了一系列下游效应。
