News & Events
Caryn E. Outten, Ph.D.
Posted on November 19, 2021
Date - November 19, 2021
1:00 pm - 2:00 pm
Guy F. Lipscomb Professor of Chemistry
Department of Chemistry and Biochemistry
University of South Carolina
Talk Title: Finding Iron Balance – The Ups and Downs of Iron Regulation in Yeast
Iron homeostasis in all cells involves balancing iron uptake and storage with iron utilization to achieve adequate, non-toxic levels of this essential nutrient. In humans, dysregulation of iron metabolism can lead to diseases such as anemia, iron overload disorders, and neurodegenerative diseases. To better understand iron regulation at the cellular and molecular level, our research group is teasing out the mechanistic details of iron sensing and regulation using yeast model systems.1 Our studies are focused on characterizing the roles of monothiol glutaredoxins Grx3/Grx4 that bind iron-sulfur (Fe-S) clusters with BolA partner proteins. Monothiol Grxs and BolA proteins have close homologues in bacteria and higher eukaryotes (including humans), but their specific functions have been best characterized in yeast. These binding partners together regulate the function of different yeast transcription factors that control iron uptake, storage, and utilization genes. Using a combination of protein biochemistry, spectroscopy, mutagenesis, and yeast genetics and cell biology, we have demonstrated how Grx3/4 and Bol2 proteins signal and control iron bioavailability in yeast via Fe-S cluster trafficking and transfer.2 We have identified residues in Grx3/4, Bol2, and their transcription factor targets that play key roles in donor-target recognition and influence Fe-S cluster binding and transfer rates. Taken together, these studies provide a detailed picture of the dynamic interactions between these Fe-S binding partners that govern iron regulation in yeast, and demonstrate that Grxs and BolA proteins have evolutionarily conserved roles in iron regulation.
1. Gupta, M., and Outten, C. E. (2020) Iron-sulfur cluster signaling: the common thread in fungal iron regulation, Curr Opin Chem Biol 55, 189-201.
2. Talib, E. A., and Outten, C. E. (2021) Iron-sulfur cluster biogenesis, trafficking, and signaling: roles for CGFS glutaredoxins and BolA proteins, Biochim Biophys Acta Mol Cell Res 1868, 118847.