Cited by 148Metalloenzymes and iron-sulfur proteinsEnzyme Structure and FunctionMitochondrial Function and Pathology

Mammalian Frataxin Controls Sulfur Production and Iron Entry during de Novo Fe 4 S 4 Cluster Assembly

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Colin, Florent, Martelli, Alain, Clémancey, Martin, Latour, Jean-Marc, Gambarelli, Serge, Zeppieri, Laura, Birck, Catherine, Page, Adeline +2 more·2013·Journal of the American Chemical Society

Abstract

Iron-sulfur (Fe-S) cluster-containing proteins are essential components of cells. In eukaryotes, Fe-S clusters are synthesized by the mitochondrial iron-sulfur cluster (ISC) machinery and the cytosolic iron-sulfur assembly (CIA) system. In the mammalian ISC machinery, preassembly of the Fe-S cluster on the scaffold protein (ISCU) involves a cysteine desulfurase complex (NFS1/ISD11) and frataxin (FXN), the protein deficient in Friedreich's ataxia. Here, by comparing the biochemical and spectroscopic properties of quaternary (ISCU/NFS1/ISD11/FXN) and ternary (ISCU/NFS1/ISD11) complexes, we show that FXN stabilizes the quaternary complex and controls iron entry to the complex through activation of cysteine desulfurization. Furthermore, we show for the first time that in the presence of iron and L-cysteine, an [Fe(4)S(4)] cluster is formed within the quaternary complex that can be transferred to mammalian aconitase (mACO2) to generate an active enzyme. In the absence of FXN, although the ternary complex can assemble an Fe-S cluster, the cluster is inefficiently transferred to ACO2. Taken together, these data help to unravel further the Fe-S cluster assembly process and the molecular basis of Friedreich's ataxia.

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Crossref · 10.1021/ja308736e

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  • Frataxin has been identified as an important iron regulator of Fe-S biogenesis.

    “The Fe source of the cluster is not yet known, although frataxin (FXN) has been identified as an important iron regulator of Fe-S biogenesis (Colin et al., 2013).”

    From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Colin et al., 2013

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Authors
Colin, F., Martelli, A., Clémancey, M., Latour, J.-M., Gambarelli, S., Zeppieri, L., Birck, C., Page, A., Puccio, H., & Ollagnier de Choudens, S.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Université Joseph Fourier (FR)
  • DSV/iRTSV/CBM, UMR 5249 CEA-Université Grenoble I-CNRS/Equipe Biocatalyse, CEA-Grenoble, 17 Rue des Martyrs, 38054 Grenoble Cedex 09, France
Corresponding author
Puccio, Hélène
Venue
Journal of the American Chemical Society
Published
2013-01-07
Volume
135
Issue
2
Pages
733-740
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
OpenAlex
W2065331957
Cited by
148
References
48
Citations by year
2026: 1 · 2025: 5 · 2024: 12 · 2023: 2 · 2022: 13 · 2021: 11 · 2020: 6 · 2019: 16 · 2018: 19 · 2017: 14 · 2016: 7 · 2015: 13 · 2014: 19 · 2013: 10
FWCI
5.15
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of the American Chemical Society (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Topics
  • Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
frataxin, iron-sulfur cluster assembly, Friedreich's ataxia, IscU, cysteine desulfurase, sulfur production, aconitase
MeSH terms
Frataxin, Animals, Humans, Iron, Iron-Sulfur Proteins, Models, Molecular, Sulfur, Iron-Binding Proteins, Coordination Complexes

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