Nuclear genomic control of mitochondrial DNA heteroplasmy in humans: population genetics and disease

Mitochondrial DNA (mtDNA) mutations are an important cause of inherited disease, but it is not known how they arise, nor why some mutations are more common than others. Our pilot work implicates a mechanism controlled by the nuclear genome, which acts on female egg cells during the development of an embryo.

We aim to define the mechanism of inheritance of mtDNA and understand how the cell nucleus controls it. We will find out why some mtDNA mutations are suppressed and how other mtDNA mutations are preferentially inherited. This will uncover the biology driving mtDNA genetic variation and why it sometimes causes mitochondrial diseases. In the process, we will identify new targets to treat or prevent mtDNA disorders.

Given emerging evidence linking mtDNA mutations to age-related neurodegenerative diseases, these findings will have important implications for human health in an ageing population.