Grant: New Investigator Salary Award - PA: Regional Partnerships Program - Saskatchewan

Mitochondria are small compartments within the cell that make ATP, the chemical form of energy that supports normal cell function. ATP is produced by the concerted effort of a number of enzyme complexes. One of these enzyme complexes, called cytochrome c oxidase (COX), requires copper for its activity, and an inability to deliver copper to the enzyme during its assembly results in a severe COX deficiency, and causes muscle, heart, liver and brain disease in children. I recently discovered that Synthesis of Cytochrome c Oxidase 1 (SCO1) and SCO2, two of the many proteins that deliver copper to COX, also fulfill novel and unexpected roles in regulating how copper is handled elsewhere in the cell. This additional function likely serves to minimize the potential toxicity of copper as it is transported, and ensure that it is appropriately distributed throughout the cell; however, much remains to be learned about how this process is coordinated and, in particular, how SCO proteins communicate with other proteins found elsewhere in the cell to ultimately control how copper is handled. Therefore, the overall goal of my research proposal is to use cultured patient cells and transgenic mouse models as tools to identify and characterize the various components of this pathway. By doing so, we will understand much more about how mitochondria make fundamental contributions to the safe handling and appropriate distribution of copper throughout the cell and, indeed, the entire body. This in turn may lead to the development of novel therapies with which to treat human diseases that result from an isolated COX deficiency or cellular copper handling defects, which are currently lacking.