Grant: Project Grant

Mitochondria are the power plants of our cells, converting the food that we eat into energy needed to survive. Thus, it should come as no surprise that mitochondrial dysfunction can have adverse effects on human health. Mitochondrial disease is a rare, though not uncommon, difficult to diagnose genetic disorder, caused by mitochondrial dysfunction. At present there are no cures, and treatment is mostly to manage symptoms. As such, fewer than 50% of diagnosed children survive to adulthood. However, a genetic diagnosis of disease is of immense value to both clinicians as well as patients and their families. While recent advances in genetic analyses have accelerated mitochondrial disease diagnosis, by helping to identify mutations in genes causing mitochondrial dysfunction, a definitive answer is found less than half of the time. When novel candidate disease genes and mutations are identified, they require additional functional validation. Such work can take significant time and effort, and has created a bottleneck in diagnosing mitochondrial disease patients. Thus, it is imperative to evaluate these candidate mutations. In addition to providing a genetic diagnosis, characterizing these novel disease-causing mutations helps to identify the underlying cause of mitochondrial dysfunction, which provides fundamental insight and understanding of the molecular mechanisms regulating mitochondria. This insight is essential groundwork prior to developing a cure for mitochondrial disease. By employing methods and approaches that allow us to characterize mitochondrial dysfunction, our research will help provide clinical diagnoses for patients with mitochondrial disease, and deliver a better understanding of the mechanisms regulating mitochondrial function. Given the growing appreciation for the role mitochondria play in human health and disease, our research has both short and long-term benefits to Canadians and the Canadian health care system.