This is a project which is currently making use of HPC facilities at Newcastle University. It is active.
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Mitochondrial DNA mutations accumulate with age in both dividing and non‑dividing tissues, yet in individuals with inherited mtDNA diseases these mutations decline over time, specifically in mitotic tissues. This study explores the basis of this phenomenon using a mouse model carrying the heteroplasmic m.5024C>T mutation.
In multiple mitotic tissues, the mutation load decreases at a rate proportional to each tissue’s turnover. This decline is not explained by altered apoptosis, but may instead reflect an upper threshold of tolerated mutation load within stem cell populations and the influence of cellular proliferation dynamics. In contrast, post‑mitotic tissues retain stable mutation levels over time.
Previous computational modelling indicates that rapid mtDNA replication and segregation during cell division accelerates genetic drift in mitotic tissues, providing a plausible mechanism for the observed reduction. This study aims to clarify how mtDNA mutations behave across different tissue types and offer insight into the development of mitochondrial disease phenotypes.