Grant: CIHR Fellowship

Mitochondrial diseases (MDs) are both the largest and the most common group of rare genetic diseases in humans, many of which go without diagnosis and treatment. The first step towards treatment of these diseases is the accurate identification and characterization of the gene responsible for the particular disorder. Genome sequencing an essential tool in disease gene identification, utilized in this proposal, but the ensuing characterization of that potential gene often lacks the advanced techniques utilized in more basic research. Here, we propose to identify and characterize novel mitochondrial disease genes, implementing new techniques used basic research to this translational research setting. In addition, we propose to investigate the mechanisms regulating mitochondrial DNA depletion, a common theme in many diseases, within a subset of our mitochondrial disease patient-derived cell lines. We believe our results could lead to more patient-tailored therapies, as well as uncover new and better characterize already discovered mitochondrial diseases. Finally, while mitochondrial dysfunction underlies a large number of other human diseases, including neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, uncovering the mechanisms governing mitochondrial dysfunction could result in the discovery of novel targetable pathways to increase mitochondrial health in these diseases.