With this award, the Chemistry of Life Processes in the Chemistry Division is funding Dr. Mary E. Konkle (Department of Chemistry, Eastern Illinois University), Dr. Michael A. Menze (Department of Biological Sciences, Eastern Illinois University), and Dr. Nilay Chakraborty (Department of Engineering, University of Michigan-Dearborn) to investigate the novel chemical properties of the recently described human protein mitoNEET and their impact on life processes. Energy can be produced through different pathways in cells. How the traffic of fuel through these pathways is directed is still unclear. Evidence suggests that mitoNEET, a novel iron-sulfur containing human protein, regulates the flow of fuel through different pathways in a tissue specific manner. This role directly links chemistry of iron-sulfur proteins to the life process of energy generation. Our integrated approach combines techniques from biochemistry, molecular biology, and bioengineering to address the role of mitoNEET in cells. Students are acquiring training in protein expression, genetic engineering, and cellular imaging provided by the three participating laboratories. Furthermore, the Investigators are extending outreach opportunities to high school students and teachers. This collaboration gives students access to cutting edge molecular research while simultaneously encourages development of diverse talent in the science and engineering pipeline.
MitoNEET was discovered as the first member of the [2Fe-2S]-containing family of CISD proteins in 2004, but the biochemical and physiological function(s) of these proteins are still ill-defined. Knockdown models of mitoNEET have shown that this protein impacts the generation of ATP by oxidative phosphorylation (OXPHOS) in a tissue specific manner. The central hypothesis of this project is that the oxidation state and association of mitoNEET with dehydrogenase enzymes constitutes a tissue specific link between cellular energy metabolism and iron redox chemistry. In three different cell types, the cellular distribution of oxidized and reduced mitoNEET is characterized with the use of Raman interferometry. In addition, the impact of mitoNEET binding on allosteric control of glutamate dehydrogenase 1 and the cellular functions of cytoplasmic glyceraldehyde-3-phosphate dehydrogenase are characterized through a range of cellular experiments. The project goals are to elucidate the mechanisms by which mitoNEET modulates cellular energy production through regulation of iron homeostasis and control of carbon flux through dehydrogenase enzymes in various tissue types.
