Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron-sulfur proteins

  1. Marta A Uzarska
  2. Veronica Nasta
  3. Benjamin D Weiler
  4. Farah Spantgar
  5. Simone Ciofi-Baffoni
  6. Maria Rosaria Saviello
  7. Leonardo Gonnelli
  8. Ulrich Mühlenhoff
  9. Lucia Banci  Is a corresponding author
  10. Roland Lill  Is a corresponding author
  1. Philipps-Universität, Germany
  2. University of Florence, Italy
  3. Philipps-Universität Marburg, Germany

Abstract

Assembly of mitochondrial iron-sulfur (Fe/S) proteins is a key process of cells, and defects cause many rare diseases. In the first phase of this pathway, ten Fe/S cluster (ISC) assembly components synthesize and insert [2Fe-2S] clusters. The second phase is dedicated to the assembly of [4Fe-4S] proteins, yet this part is poorly understood. Here, we characterize the BOLA family proteins Bol1 and Bol3 as specific mitochondrial ISC assembly factors that facilitate [4Fe-4S] cluster insertion into a subset of mitochondrial proteins such as lipoate synthase and succinate dehydrogenase. Bol1-Bol3 perform largely overlapping functions, yet cannot replace the ISC protein Nfu1 that also participates in this phase of Fe/S protein biogenesis. Bol1 and Bol3 form dimeric complexes with both monothiol glutaredoxin Grx5 and Nfu1. Complex formation differentially influences the stability of the Grx5-Bol-shared Fe/S clusters. Our findings provide the biochemical basis for explaining the pathological phenotypes of patients with mutations in BOLA3.

Article and author information

Author details

  1. Marta A Uzarska

    Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Veronica Nasta

    Magnetic Resonance Center CERM, University of Florence, Florence, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Benjamin D Weiler

    Institut für Zytobiologie, Philipps-Universität Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Farah Spantgar

    Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Simone Ciofi-Baffoni

    Magnetic Resonance Center CERM, University of Florence, Florence, Italy
    Competing interests
    The authors declare that no competing interests exist.
  6. Maria Rosaria Saviello

    Magnetic Resonance Center CERM, University of Florence, Florence, Italy
    Competing interests
    The authors declare that no competing interests exist.
  7. Leonardo Gonnelli

    Magnetic Resonance Center CERM, University of Florence, Florence, Italy
    Competing interests
    The authors declare that no competing interests exist.
  8. Ulrich Mühlenhoff

    Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Lucia Banci

    Magnetic Resonance Center CERM, University of Florence, Florence, Italy
    For correspondence
    banci@cerm.unifi.it
    Competing interests
    The authors declare that no competing interests exist.
  10. Roland Lill

    Institut für Zytobiologie, Philipps-Universität Marburg, Marburg, Germany
    For correspondence
    lill@staff.uni-marburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8345-6518

Funding

Deutsche Forschungsgemeinschaft (SPP 1927)

  • Roland Lill

European Commission (iNEXT 653706)

  • Lucia Banci

Deutsche Forschungsgemeinschaft (SFB 987)

  • Ulrich Mühlenhoff
  • Roland Lill

European strategy forum on research infrastructures (Instruct)

  • Lucia Banci

LOEWE program of state Hesse, Germany (Synmikro)

  • Roland Lill

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2016, Uzarska et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Marta A Uzarska
  2. Veronica Nasta
  3. Benjamin D Weiler
  4. Farah Spantgar
  5. Simone Ciofi-Baffoni
  6. Maria Rosaria Saviello
  7. Leonardo Gonnelli
  8. Ulrich Mühlenhoff
  9. Lucia Banci
  10. Roland Lill
(2016)
Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron-sulfur proteins
eLife 5:e16673.
https://doi.org/10.7554/eLife.16673

Share this article

https://doi.org/10.7554/eLife.16673

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