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Chromosome biology

Mixing it up

Nature Reviews Molecular Cell Biology volume 13, pages 750–751 (2012)Cite this article

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To investigate the underlying basis of mtDNA uniparental inheritance, Sharpley et al. generated mice carrying two normal but different mouse mtDNAs (heteroplasmy), one from 129 mice and the other from NZB mice, which were maintained on a C57BL/6J nuclear background. Offspring from each generation were genotyped at weaning and throughout life. Although the proportion of the two mtDNAs was relatively stable in the brain, heart and muscle, the NZB mtDNAs were progressively enriched in the liver but progressively lost in the spleen, pancreas, ovary and along the female germ line through successive generations. Hence, mtDNA heteroplasmy is directionally eliminated from animal tissues and the female germ line.

So why is uniparental mtDNA inheritance favoured? Sharpley et al. found that mice harbouring both 129 and NZB mtDNAs showed a significant reduction in metabolic rate, reduced activity and feeding, hyperexcitability and a decreased capacity to learn and remember, whereas mice with only 129 or NZB mtDNAs were normal. One possible reason for this effect could be that the assembly of multi-polypeptide complexes involved in oxidative phosphorylation using polypeptides with two different amino acid sequences may reduce energetic efficiency which preferentially affects the highly oxidative brain. As human and animal mtDNAs are highly polymorphic, heteroplasmic mtDNA incompatibility could provide the selective pressure for uniparental inheritance.

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ORIGINAL RESEARCH PAPERS

  1. Sharpley, M. S. et al. Heteroplasmy of mouse mtDNA is genetically unstable and results in altered behavior and cognition. Cell 151, 333–343 (2012)

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  2. Tachibana, M. et al. Towards germline gene therapy of inherited mitochondrial diseases. 24 Oct 2012 Nature (doi:10.1038/nature11647)

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  1. Bryony Jones
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Jones, B. Mixing it up. Nat Rev Mol Cell Biol 13, 750–751 (2012). https://doi.org/10.1038/nrm3476

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  • DOI: https://doi.org/10.1038/nrm3476

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