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Presenter: Observation Sael Lee Title: Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing A. Latorre-Pellicer et al. Nature (2016) doi:10.1038/nature18618 Problem: Problem: Human mitochondrial DNA (mtDNA) has high within-population sequence variability. Although lacking molecular level evidence, mtDNA may be involved in ageing or diseases and mitochondrial replacement has the potential to prevent mtDNA related disease. However, this technology requires a understanding of the physiological relevance of mtDNA sequence variability and its match with in mitochondrial genes. Challenges: Previous studies in conplastic animals allow comparison of individuals with the same nuclear genome but different mtDNA variants. However, most of these studies did not confirm the conplastic status, focused on younger animals, and did not investigate the full range of physiological and phenotypic variability likely to be influenced by mitochondria. Key Words: mtDNA, diseases, conplastic animals SUNY Korea BioData Mining Lab - Journal Review 1/3 Solution Solution Approach: Approach: They systematically characterized conplastic mice throughout their lifespan using transcriptomic, proteomic, metabolomic, biochemical, physiological and phenotyping studies. That is, they transferred mtDNA from a mouse strain called NZB to the nuclear DNA (nDNA) background of another strain, C57BL/6, and then compared C57BL/6 mice that harboured NZB or C57BL/6 mtDNA. Comparison of the mice throughout their lives revealed huge differences in mitochondrial function, insulin signalling, obesity and longevity. Results: Results: : They show that mtDNA haplotype influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains. This shows that naturally occurring mtDNA variation is not neutral, and that the interaction between mtDNA sequence variants and nDNA can have profound effects on mammalian biology. Also, the amount of variation between NZB and C57BL/6 mtDNAs is about the same as that between two unrelated human mtDNAs, so mtDNA variation and its effect on nDNA gene expression is also relevant to people. SUNY Korea BioData Mining Lab - Journal Review 2/3 Representative Figure(s) BioDM BioDM Lab Lab Take-ins: Take-ins: Many of the current mtDNAs are discarded in the genome analysis. However, analysis of mtDNA and disease is interesting and should not be discarded. *Notes: paper introduce in “Genetics: Mitochondrial DNA in evolution and disease” Nature (2016) doi:10.1038/nature18902 by D. Wallace SUNY Korea BioData Mining Lab - Journal Review 3/3