Mitochondrial Dysfunction in Cancer

While the importance of mitochondria in normal cell biology has long been recognized, we have not yet examined the significance of changes in mitochondrial mass for predicting cancer progression or therapy response. In the proposed work, we will examine whether we can use the number of mitochondria and an estimation of their function to predict how tumors will progress, and whether they are likely to be responsive to conventional therapies.

We will also examine whether we can specifically kill tumor cells by disrupting mitophagy, the selective removal of damaged mitochondria from cancer cells before they die. In cancer cell lines, we will test small molecules that were identified in a high throughput screen of 1,200 FDA-approved drugs as having the potential to modify mitochondrial mass through mitophagy. Disrupting the removal of damaged mitochondria is predicted to block key metabolic functions upon which tumor cells are more dependent than normal cells, resulting in tumor cell death. Since the number of damaged mitochondria is less in normal cells compared to tumor cells, we predict that normal cells would be resistant to such drugs, limiting the toxicity of potential novel therapies that arise from this study.