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Nat Commun. 2014 Oct 31;5:5013. doi: 10.1038/ncomms6013.

Functional reconstitution of mitochondrial Fe/S cluster synthesis on Isu1 reveals the involvement of ferredoxin.

Author information

1
Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, 35032 Marburg, Germany.
2
CERM, Magnetic Resonance Center, University of Florence, Sesto Fiorentino, 50019 Florence, Italy.
3
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Street, 35043 Marburg, Germany.
4
Biochemie-Zentrum Heidelberg (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
5
1] CERM, Magnetic Resonance Center, University of Florence, Sesto Fiorentino, 50019 Florence, Italy [2] Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy.
6
1] Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, 35032 Marburg, Germany [2] Max-Planck-Institut für terrestrische Mikrobiologie, Karl-von-Frisch-Street 10, 35043 Marburg, Germany [3] LOEWE Zentrum für Synthetische Mikrobiologie SynMikro, Hans-Meerwein-Street, 35043 Marburg, Germany.

Abstract

Maturation of iron-sulphur (Fe/S) proteins involves complex biosynthetic machinery. In vivo synthesis of [2Fe-2S] clusters on the mitochondrial scaffold protein Isu1 requires the cysteine desulphurase complex Nfs1-Isd11, frataxin, ferredoxin Yah1 and its reductase Arh1. The roles of Yah1-Arh1 have remained enigmatic, because they are not required for in vitro Fe/S cluster assembly. Here, we reconstitute [2Fe-2S] cluster synthesis on Isu1 in a reaction depending on Nfs1-Isd11, frataxin, Yah1, Arh1 and NADPH. Unlike in the bacterial system, frataxin is an essential part of Fe/S cluster biosynthesis and is required simultaneously and stoichiometrically to Yah1. Reduced but not oxidized Yah1 tightly interacts with apo-Isu1 indicating a dynamic interaction between Yah1-apo-Isu1. Nuclear magnetic resonance structural studies identify the Yah1-apo-Isu1 interaction surface and suggest a pathway for electron flow from reduced ferredoxin to Isu1. Together, our study defines the molecular function of the ferredoxin Yah1 and its human orthologue FDX2 in mitochondrial Fe/S cluster synthesis.

PMID:
25358379
DOI:
10.1038/ncomms6013
[Indexed for MEDLINE]

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