Grant: Doctoral Research Award - PA: Mitochondrial Disease (SHOPP)

Our body is made up of millions of cells. Each cell requires energy to function and they must convert the nutrients in our diet to ATP, the form of energy each cell uses. In most cells, specialized compartments called mitochondria perform the majority of this conversion. Mitochondria contain much of the genetic information required to create ATP. So if there is a mutation in this genetic information, the mitochondria cannot produce sufficient ATP. Cells will lack the energy to fully operate and devastating disorders, termed mitochondrial diseases, are the result. This proposed research aims to use a drug, AICAR, to therapeutically treat these disorders. AICAR is unique because, by activating AMP-Activated Protein Kinase (AMPK), it can both activate the creation of new mitochondria and breakdown dysfunctional mitochondria. By activating mitochondrial growth and increasing the ratio of mitochondria that can efficiently make energy, the energy production capacity is restored to levels of healthy cells. Breaking down the dysfunctional mitochondria can prevent the proliferation of poor energy producing mitochondria and improve the overall energy producing capacity of each mitochondrion in the cell. This study will use AICAR to treat skin cells from patients who suffer from these disorders. We will then take functional measurements of the cells to look for improvements and, if found, analyze the origin of these improvements. We hypothesize that this will improve the functional capacity of the cells as indicated by their energy producing potential.