N01 - Roles of differentially localized glutaredoxin 2 isoforms (N01)

• Fachliche Zuordnung: Biochemie
• Förderung: Förderung von 2007 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5485539

Redox signaling events are increasingly recognized as major determinants of cellularfunctions and glutaredoxins play a central role in the transfer of these redox signals. MammalianGrx2 was first identified in mitochondria, where it fulfills a central role in the response ofthe cell tooxidative challenges and apoptotic stimuli. We identified Grx2 as first iron-sulfiir cluster protein ofthe thioredoxin family. Today, an increasing number of additional iron-sulfiir glutaredoxins hasbeen described with suggested functions in redox signaling and iron-sulfiir cluster biogenesis. Theresults of our efforts during the fist three years of funding indicate new functions of glutaredoxins insome central aspects of cell biology. The mechanism of iron-sulfur cluster binding to Grxs wasclarified and we were able to demonstrate that this mode of iron binding is indispensable for anessential function of the yeast iron-sulfur glutaredoxins Grx3/Grx4 in one of the most central tasksin cellular iron metabolism - the trafficking and delivery of iron in the cytosol. We have identifiedcytosolic Grx2 isoforms in both human and mouse and propose a role ofone ofthese proteins in theregulation of cytoskeletal dynamics, cell migration, and the differentiation of neurons. Potentialtargets of Grx2 redox regulation were identified and some of them may provide the link to themolecular understanding of these functions. Our work during the proposed 5* year of funding willthus focus on the mechanisms of these processes and their physiological significance. We envisionthat our studies will provide new insights into basic cellular processes, namely the trafficking ofiron through the cytosol and the regulation of cytoskeletal dynamics.

• DFG-Verfahren: Sonderforschungsbereiche
• Teilprojekt zu: SFB 593: Mechanismen der zellulären Kompartimentierung und deren krankheitsrelevante Veränderungen
• Antragstellende Institution: Philipps-Universität Marburg
• Teilprojektleiter: Privatdozent Dr. Christopher Horst Lillig