Molecular mechanisms of sulfur transfer during biosynthesis of iron-sulfur clusters in eukaryotes

• Antragsteller: Dr. Torsten Heidenreich
• Fachliche Zuordnung: Biochemie
• Förderung: Förderung von 2008 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 85706514

Iron sulfur (Fe/S) clusters are inorganic cofactors of proteins with functions in catalysis, electron transfer and regulation. The biogenesis of Fe/S proteins in living organisms requires complex proteinaceous machineries. In eukaryotes mitochondria perform a primary role in biogenesis in that the ISC assembly machinery of the matrix is involved in maturation of all cellular Fe/S proteins. This machinery relies on the cysteine desulfurase Nfs1 as the sulfur donor and the scaffold Isu1/2 for initial synthesis of the Fe/S cluster. The assembly of cytosolic/nuclear Fe/S proteins additionally requires the mitochondrial ISC export apparatus and the cytosolic CIA machinery. A key reaction in Fe/S protein biosynthesis is the mobilisation of sulfur from cysteine by mitochondrial Nfs1 and its subsequent transfer to cellular Fe/S proteins via the Isu1 scaffold. For maturation of extra-mitochondrial Fe/S proteins, a yet unknown, sulfur-containing compound is exported to the cytosol. The aim of this proposal is the dissection of the biochemical mechanisms of sulfur transfer from Nfs1 to mitochondrial and extra-mitochondrial Fe/S proteins. First, the essential role of Isd11, a Nfs1 binding partner, in transfer of sulfur to Isu1/2 will be analysed. Second, the sulfur-containing compound exported from mitochondria will be characterized and identified molecularly. The proposed work will gain significant insights into the molecular understanding of Fe/S protein biogenesis in eukaryotes.

• DFG-Verfahren: Sachbeihilfen
• Gastgeber: Professor Dr. Roland Lill