University Health Network
Blocking mitochondrial protein import and folding in acute leukemia
The mitochondria are the energy producing factories in the cell. Most of the proteins in the mitochondria are made in the cytoplasm and transported into the mitochondria through the mitochondrial protein import pathway. In our preliminary data, we demonstrated that blocking mitochondrial protein import using genetic approaches or drug-like molecules preferentially killed a subset of AML (acute myeloid leukemia) cells over normal blood cells. In this application, we will explore blocking mitochondrial protein import as a new strategy to treat leukemia. Specifically, we will study the mechanism by which blocking mitochondrial protein import kills AML cells. We will also determine whether blocking mitochondrial protein import can kill primary AML stem cells over normal cells. Finally, we will determine the effectiveness and safety of blocking mitochondrial protein import in mouse models of leukemia. Thus, through this proposal we will discover new biological insights about the role of mitochondria in AML. In addition, we will highlight a potential new treatment of this disease.