Grant: Project Grant

Mitochondria are considered the powerhouse of the cell and are essential for life. An occupational hazard of creating most of the energy for the cell is significant oxidative damage to the proteins, lipids and DNA of the mitochondrial network. Minor disruptions in mitochondrial activity as a result of this damage results in a plethora of human disorders and diseases. However, the cell has evolved an elegant and powerful mechanism to rid the cell of damaged mitochondria, termed mitophagy. Mitophagy is the specific removal of damaged mitochondria by recycling pathway called autophagy. Over the past two years we have conducted three screens to identify novel factors that regulate mitophagy in the context of human disease. First, we have identified several small molecule drugs that promote mitophagy. Second, we have identified a probiotic yeast that secretes factors to modulate mitophagy. Third, we have identified several genes not previously implicated in mitophagy but have the ability to regulate the molecular pathway. We propose to characterize the mechanism of action of these three categories of mitophagy modulators, thereby expanding our knowledge of this important basic cell biological pathway in human health and disease.