Download Title: Genetics: Mitochondrial DNA in evolution and disease Douglas

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
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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.
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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
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