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Licensed Unlicensed Requires Authentication Published by De Gruyter April 17, 2020

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

  • Roland Lill

    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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From the journal Biological Chemistry

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.

About the author

Roland Lill

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.

Acknowledgments

I thank the members of my group for their great work, and Dr. S.A. Freibert for help with the Figures. Generous financial support from the Deutsche Forschungsgemeinschaft, Funder Id: http://dx.doi.org/10.13039/501100001659 (Koselleck grant LI 415/6, LI 415/5, SFB 987, SPP 1710, and SPP 1927), German-Israeli Foundation GIF, Funder Id: http://dx.doi.org/10.13039/501100001736, Grant Number: I-1302-412.13/2015, COST Action FeSBioNet, Funder Id: http://dx.doi.org/10.13039/501100000921 (Contract CA15133), and Volkswagen Foundation, Funder Id: http://dx.doi.org/10.13039/501100001663 (‘Life’ program) is acknowledged.

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Received: 2020-01-27
Accepted: 2020-03-10
Published Online: 2020-04-17
Published in Print: 2020-05-26

©2020 Walter de Gruyter GmbH, Berlin/Boston

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