Aurora kinase A localises to mitochondria to control organelle dynamics and energy production

  1. Giulia Bertolin  Is a corresponding author
  2. Anne-Laure Bulteau
  3. Marie-Clotilde Alves-Guerra
  4. Agnes Burel
  5. Marie-Thérèse Lavault
  6. Olivia Gavard
  7. Stephanie Le Bras
  8. Jean-Philippe Gagné
  9. Guy G Poirier
  10. Roland Le Borgne
  11. Claude Prigent  Is a corresponding author
  12. Marc Tramier  Is a corresponding author
  1. CNRS, UMR 6290, France
  2. ENS Lyon, France
  3. Inserm U1016, Institut Cochin, France
  4. UMS CNRS 3480- US INSERM 018, Université de Rennes 1, France
  5. Laval University, Canada

Abstract

Many epithelial cancers show cell cycle dysfunction tightly correlated with the overexpression of the serine/threonine kinase Aurora A (AURKA). Its role in mitotic progression has been extensively characterised, and evidence for new AURKA functions emerges. Here, we reveal that AURKA is located and imported in mitochondria in several human cancer cell lines. Mitochondrial AURKA impacts on two organelle functions: mitochondrial dynamics and energy production. When AURKA is expressed at endogenous levels during interphase, it induces mitochondrial fragmentation independently from RALA. Conversely, AURKA enhances mitochondrial fusion and ATP production when it is over-expressed. We demonstrate that AURKA directly regulates mitochondrial functions and that AURKA over-expression promotes metabolic reprogramming by increasing mitochondrial interconnectivity. Our work paves the way to anti-cancer therapeutics based on the simultaneous targeting of mitochondrial functions and AURKA inhibition.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Giulia Bertolin

    CNRS, UMR 6290, Rennes, France
    For correspondence
    giulia.bertolin@univ-rennes1.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7359-5733
  2. Anne-Laure Bulteau

    ENS Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Marie-Clotilde Alves-Guerra

    Inserm U1016, Institut Cochin, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Agnes Burel

    Microscopy Rennes Imaging Centre, SFR Biosit, UMS CNRS 3480- US INSERM 018, Université de Rennes 1, Rennes, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Marie-Thérèse Lavault

    Microscopy Rennes Imaging Centre, SFR Biosit, UMS CNRS 3480- US INSERM 018, Université de Rennes 1, Rennes, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Olivia Gavard

    CNRS, UMR 6290, Rennes, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephanie Le Bras

    CNRS, UMR 6290, Rennes, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Jean-Philippe Gagné

    Centre de Recherche du CHU de Quebec, Laval University, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Guy G Poirier

    Centre de recherche du CHU de Quebec, Laval University, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Roland Le Borgne

    CNRS, UMR 6290, Rennes, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6892-278X
  11. Claude Prigent

    CNRS, UMR 6290, Rennes, France
    For correspondence
    claude.prigent@univ-rennes1.fr
    Competing interests
    The authors declare that no competing interests exist.
  12. Marc Tramier

    CNRS, UMR 6290, Rennes, France
    For correspondence
    marc.tramier@univ-rennes1.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8200-6446

Funding

ARC (post-doc grant)

  • Giulia Bertolin

Ligue Contre le Cancer (Grand ouest gant)

  • Marc Tramier

Fondation Tourre (post-doc gant)

  • Giulia Bertolin

Agence Nationale de la Recherche (KinBioFRET)

  • Roland Le Borgne
  • Claude Prigent
  • Marc Tramier

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

Reviewing Editor

  1. Jody Rosenblatt, University of Utah, United States

Publication history

  1. Received: May 4, 2018
  2. Accepted: August 1, 2018
  3. Accepted Manuscript published: August 2, 2018 (version 1)
  4. Version of Record published: September 14, 2018 (version 2)

Copyright

© 2018, Bertolin 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. Giulia Bertolin
  2. Anne-Laure Bulteau
  3. Marie-Clotilde Alves-Guerra
  4. Agnes Burel
  5. Marie-Thérèse Lavault
  6. Olivia Gavard
  7. Stephanie Le Bras
  8. Jean-Philippe Gagné
  9. Guy G Poirier
  10. Roland Le Borgne
  11. Claude Prigent
  12. Marc Tramier
(2018)
Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
eLife 7:e38111.
https://doi.org/10.7554/eLife.38111

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