1. Biochemistry
  2. Cell Biology
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Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals

  1. Inge Kühl Is a corresponding author
  2. Maria Miranda
  3. Ilian Atanassov
  4. Irina Kuznetsova
  5. Yvonne Hinze
  6. Arnaud Mourier
  7. Aleksandra Filipovska
  8. Nils-Göran Larsson Is a corresponding author
  1. Max Planck Institute for Biology of Ageing, Germany
  2. The University of Western Australia, Australia
  3. Université de Bordeaux, France
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Cite as: eLife 2017;6:e30952 doi: 10.7554/eLife.30952

Abstract

Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment.

Article and author information

Author details

  1. Inge Kühl

    Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany
    For correspondence
    kuehl@age.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-4797-0859
  2. Maria Miranda

    Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Ilian Atanassov

    Proteomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-8259-2545
  4. Irina Kuznetsova

    Harry Perkins Institute of Medical Research, The University of Western Australia, Nedlands, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Yvonne Hinze

    Proteomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Arnaud Mourier

    Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Aleksandra Filipovska

    Harry Perkins Institute of Medical Research, The University of Western Australia, Nedlands, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-6998-8403
  8. Nils-Göran Larsson

    Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany
    For correspondence
    Larsson@age.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-5100-996X

Funding

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

Ethics

Animal experimentation: The health status of the animals is specific pathogen free according to the Federation of the European Laboratory Animal Science Association (FELASA) recommendations. All animal procedures were conducted in accordance with European, national and institutional guidelines and protocols (no.: AZ.: 84-02.05.50.15.004 and AZ.: 84-02.04.2015.A103) were approved by the Landesamt für Natur, Umwelt und Verbraucherschutz, Nordrhein-Westfalen, Germany.

Reviewing Editor

  1. Agnieszka Chacinska, Reviewing Editor, University of Warsaw, Poland

Publication history

  1. Received: August 1, 2017
  2. Accepted: November 6, 2017
  3. Accepted Manuscript published: November 14, 2017 (version 1)

Copyright

© 2017, Kühl 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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