Grant: Operating Grant

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 enzymes. One of these enzymes, called cytochrome c oxidase (COX), requires copper for its activity. An inability to deliver copper to COX results in a severe deficiency in this enzyme, and causes muscle, heart, liver and brain disease in children. Copper is delivered to COX by many proteins, three of which also fulfill novel and unexpected roles in controlling how proteins localized elsewhere in the cell handle copper. This additional function likely serves to minimize the potential toxicity of copper as it is transported, and ensure that copper is appropriately distributed throughout the cell. Much remains to be learned, however, about how mitochondrial proteins communicate with other cellular proteins to control global copper handling. To better understand this dialogue, my lab studies a variety of applicable cell culture and animal models. By doing so, we will appreciate 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 innovative therapies for the effective treatment of human diseases caused by defects in the associated copper handling pathways, which are currently lacking.