Maternally inherited mitochondrial disease are uniquely hard to manage because of a unique feature called heteroplasmy. Mutant and normal mitochondrial DNA (mtDNA) coexist in patients with heteroplasmic mtDNA disease. The load of mutant mtDNA is a key determinant of severity and of the remarkably variable transmission of mutant mtDNA to the offspring. Pre-implantation genetic screening and mitochondrial replacement therapy may enable patients to have healthy offspring.

Mitophagy is a cellular mechanism for recycling damaged mitochondria. It is one of the factors held to reduce the mutant mtDNA that accumulates in patient tissues and underlies progressive symptoms. Nevertheless, whether mitophagy is important in vivo is completely unknown.

We have developed high throughput imaging and shown, for the first time, that mitophagy is commonplace in mitochondrial diseases. We are developing drug modulators of mitophagy both as potential novel treatments for disease and for preventing mutant mtDNA transmission.