My research interest has focused on iron-sulfur proteins. Iron-sulfur proteins are involved in diverse physiological processes such as energy metabolism, DNA replication and repair, transcription regulation, and translation processes. However, the biogenesis of iron-sulfur clusters and specific functions of iron-sulfur proteins are not fully understood. My research has primarily focused on iron-sulfur cluster biogenesis and regulatory functions of iron-sulfur proteins. Our recent research has focused on mitochondrial outer membrane protein mitoNEET. MitoNEET binds a redox active [2Fe-2S] cluster in the C-terminal cytosolic domain. It was initially identified as a target of type II diabetes drug pioglitazone. Abnormal expression of mitoNEET has been associated with various cancer, diabetes, and neurodegenerative diseases. Increasing evidence has suggested that mitoNEET has an essential role in regulating energy metabolism, iron homeostasis, and production of reactive oxygen species in mitochondria. Our research has established that mitoNEET acts as a novel redox enzyme, has a specific binding site for flavin mononucleotide (FMN) and can transfer electrons from FMNH2 to oxygen or ubiquinone-10. Because FMN is reduced to FMNH2 by flavin reductase using NADH as electron donors, and NAD+ is the major product of glycolysis, we proposed that mitoNEET may promote glycolysis in human cells by oxidizing FMNH2. In this proposal, we will collaborate with Dr. Qiang Shen at LSU Medical School to explore the specific role of mitoNEET in breast cancer. MitoNEET is highly expressed in breast cancer cells and depletion of mitoNEET inhibits proliferation of the cancer cells. Our goal is to identify mitoNEET as an oncogene in breast cancer and to determine the physiological function of mitoNEET in breast cancer cells. Working together with Dr. Qiang Shen, we have the experience, expertise, necessary resources, and motivation to complete the proposed research project.
