From the discovery to molecular understanding of cellular iron-sulfur protein biogenesis

  • 1 Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, D-35032 Marburg, Germany
  • 2 SYNMIKRO Center for Synthetic Microbiology, Philipps-Universität Marburg, Hans-Meerwein-Str., D-35043 Marburg, Germany
Roland LillORCID iD: https://orcid.org/0000-0002-8345-6518
  • Corresponding author
  • Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, D-35032 Marburg, Germany
  • SYNMIKRO Center for Synthetic Microbiology, Philipps-Universität Marburg, Hans-Meerwein-Str., D-35043 Marburg, Germany
  • orcid.org/0000-0002-8345-6518
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  • Further information
  • Roland Lill is a Professor for Cell Biology and Biochemistry and Head of the Institut für Zytobiologie at the Philipps-Universität Marburg. After the discovery of eukaryotic Fe/S protein biogenesis as a catalyzed process in 1999, he concentrated his work on the identification of the machinery and the elucidation of the molecular mechanisms of this essential process of life. Lill also works on evolutionary aspects connected to Fe/S protein biogenesis in mitochondria-related organelles such as mitosomes. He is an elected member of the European Molecular Biology Organization (EMBO), and serves as a senator for the Deutsche Forschungsgemeinschaft (DFG) and the German Academy of Sciences Leopoldina.
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Abstract

Protein cofactors often are the business ends of proteins, and are either synthesized inside cells or are taken up from the nutrition. A cofactor that strictly needs to be synthesized by cells is the iron-sulfur (Fe/S) cluster. This evolutionary ancient compound performs numerous biochemical functions including electron transfer, catalysis, sulfur mobilization, regulation and protein stabilization. Since the discovery of eukaryotic Fe/S protein biogenesis two decades ago, more than 30 biogenesis factors have been identified in mitochondria and cytosol. They support the synthesis, trafficking and target-specific insertion of Fe/S clusters. In this review, I first summarize what led to the initial discovery of Fe/S protein biogenesis in yeast. I then discuss the function and localization of Fe/S proteins in (non-green) eukaryotes. The major part of the review provides a detailed synopsis of the three major steps of mitochondrial Fe/S protein biogenesis, i.e. the de novo synthesis of a [2Fe-2S] cluster on a scaffold protein, the Hsp70 chaperone-mediated transfer of the cluster and integration into [2Fe-2S] recipient apoproteins, and the reductive fusion of [2Fe-2S] to [4Fe-4S] clusters and their subsequent assembly into target apoproteins. Finally, I summarize the current knowledge of the mechanisms underlying the maturation of cytosolic and nuclear Fe/S proteins.

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