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Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis

Nature Chemical Biology volume 6, pages 758–765 (2010)Cite this article

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Abstract

Cytosolic and nuclear iron-sulfur (Fe-S) proteins play key roles in processes such as ribosome maturation, transcription and DNA repair-replication. For biosynthesis of their Fe-S clusters, a dedicated cytosolic Fe-S protein assembly (CIA) machinery is required. Here, we identify the essential flavoprotein Tah18 as a previously unrecognized CIA component and show by cell biological, biochemical and spectroscopic approaches that the complex of Tah18 and the CIA protein Dre2 is part of an electron transfer chain functioning in an early step of cytosolic Fe-S protein biogenesis. Electrons are transferred from NADPH via the FAD- and FMN-containing Tah18 to the Fe-S clusters of Dre2. This electron transfer chain is required for assembly of target but not scaffold Fe-S proteins, suggesting a need for reduction in the generation of stably inserted Fe-S clusters. The pathway is conserved in eukaryotes, as human Ndor1–Ciapin1 proteins can functionally replace yeast Tah18–Dre2.

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Figure 1: Depletion of Tah18 specifically impairs the maturation of cytosolic and nuclear Fe-S proteins.
Figure 2: Tah18 and Dre2 are required early in cytosolic Fe-S protein biogenesis.
Figure 3: Assembly of the Fe-S clusters on Dre2 requires Nfs1 but occurs independently of the CIA machinery.
Figure 4: Electron transfer from NADPH to an Fe-S cluster of Dre2 via the diflavin reductase Tah18.
Figure 5: The human Ndor1–Ciapin1 protein complex is the counterpart of yeast Tah18–Dre2.
Figure 6: The eukaryotic diflavin reductase Tah18 functions in cytosolic-nuclear Fe-S protein biogenesis.

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Acknowledgements

We thank S. Molik for plasmid construction and D. Vogel for help with cloning. We acknowledge generous support from the Deutsche Forschungsgemeinschaft (SFB 593, the Gottfried-Wilhelm Leibniz program and GRK 1216), Rhön Klinikum AG, von Behring-Röntgen Stiftung, LOEWE program of state Hessen, Max-Planck Gesellschaft and Fonds der chemischen Industrie.

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  1. Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Marburg, Germany

    Daili J A Netz, Martin Stümpfig, Carole Doré, Ulrich Mühlenhoff, Antonio J Pierik & Roland Lill

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D.J.A.N., U.M., A.J.P. and R.L. designed experiments and analyzed data. All authors performed experiments. D.J.A.N., A.J.P. and R.L. wrote the manuscript.

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Correspondence to Antonio J Pierik or Roland Lill.

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Netz, D., Stümpfig, M., Doré, C. et al. Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis. Nat Chem Biol 6, 758–765 (2010). https://doi.org/10.1038/nchembio.432

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