Mitochondrial DNA transmission and maintenance


In addition to the nuclear genome, all animals have another genome packed inside the mitochondrion called mtDNA. This maternally inherited genome encodes important proteins for energy production. During development and ageing as mtDNA continues to replicate and turnover, mutations can occur to some of the copies. The subsequent prevalence of these mutants, which determines the progression and inheritance of the clinical abnormalities of mitochondrial disorders, depends on how they compete with the co-existing wild-type genomes for transmission. To date, over 50 mtDNA-linked disorders have been described in humans.

We are interested in understanding the molecular mechanisms that govern mtDNA heteroplasmy transmission during development and ageing. In particular, we want to know why a mutant mitochondrial genome increases in abundance to cause diseases in some cases while in others, it is eliminated. By creating fruit flies carrying both functional and pathogenic mitochondrial genomes, we perform systematic and detailed studies to identify nuclear factors and mtDNA sequence polymorphisms that bias the transmission of one genome over the other to impact the progression and inheritance of mtDNA-linked disorders.

We are also interested in understanding how repair mechanisms maintain mtDNA integrity during development, how maternal inheritance of mtDNA is guaranteed and how complex mito-nuclear interactions modulate the pathogenic expression of mtDNA mutations. These studies provide insights into genome evolution, ageing and human diseases.

Principal Investigator