Is mitochondrial DNA turnover slower than commonly assumed?

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 andDNA, and the experimental data suggested highly divergent turnover rates, ranging fromover 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 tomtDNA half-life in the order ofmonths is the most consistent with published mtDNA mutation levels.