Abstract
Mutations arise during DNA replication due to oxidative lesions and intrinsic polymerase errors. Mitochondrial DNA (mtDNA) mutation rate is therefore closely linked to the mitochondrial DNA turnover process, especially in post mitotic cells. This makes the mitochondrial DNA turnover rate critical for understanding the origin and dynamics of mtDNA mutagenesis in post mitotic cells. Experimental mitochondrial turnover quantification has been based on different mitochondrial macromolecules, such as mitochondrial proteins, lipids and DNA, and the experimental data suggested highly divergent turnover rates, ranging from over 2 days to about 1 year. In this article we argue that mtDNA turnover rate cannot be as fast as is often envisaged. Using a stochastic model based on the chemical master equation, we show that a turnover rate corresponding to mtDNA half-life in the order of months is the most consistent with published mtDNA mutation levels.
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Acknowledgments
This work was supported by the Singapore Ministry of Education Grants [AcRF Tier 1, FRC Grant (R279000299112 to SKP and RG) and AcRF Tier 2 (MOE2010-T2-2-048 to SKP, JG, and BH)], Singapore and Biomedical Research Council of Singapore [Grant number: (BMRC 07/1/21/19/524 to SKP, JG and BH)], and ETH Zurich (to RG and LL).
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Suresh Kumar Poovathingal and Jan Gruber have equally contributed to this study.
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Poovathingal, S.K., Gruber, J., Lakshmanan, L. et al. Is mitochondrial DNA turnover slower than commonly assumed?. Biogerontology 13, 557–564 (2012). https://doi.org/10.1007/s10522-012-9390-7
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DOI: https://doi.org/10.1007/s10522-012-9390-7