Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells

Abstract

Recently we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0 cells) is linked to acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether transfer of mtDNA involves whole mitochondria, we injected B16ρ0 mouse melanoma cells into syngeneic C57BL/6Nsu9-DsRed2 mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration. Additionally, knockdown of key mitochondrial complex I (NDUFV1) and complex II (SDHC) subunits by shRNA in B16ρ0 cells abolished or significantly retarded their ability to form tumours. Collectively, these results show that intact mitochondria with their mtDNA payload are transferred in the developing tumour, and provide functional evidence for an essential role of oxidative phosphorylation in cancer.

Article and author information

Author details

  1. Lan-Feng Dong

    School of Medical Science, Griffith University, Southport, Australia
    For correspondence
    l.dong@griffith.edu.au
    Competing interests
    The authors declare that no competing interests exist.
  2. Jaromira Kovarova

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  3. Martina Bajzikova

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  4. Ayenachew Bezawork-Geleta

    School of Medical Science, Griffith University, Southport, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. David Svec

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Berwini Endaya

    School of Medical Science, Griffith University, Southport, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Karishma Sachaphibulkij

    School of Medical Science, Griffith University, Southport, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Ana R Coelho

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  9. Natasa Sebkova

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  10. Anna Ruzickova

    Institute of Biotechnology, Czech Academy of Science, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  11. An S Tan

    Malaghan Institute of Medical Research, Wellington, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  12. Katarina Kluckova

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  13. Kristyna Judasova

    Institute of Biotechnology, Czech Academy of Science, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  14. Katerina Zamecnikova

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  15. Zuzana Rychtarcikova

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  16. Vinod Gopalan

    School of Medical Science, Griffith University, Southport, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. Margaryta Sobol

    Institute of Molecular Genetics, Czech Academy of Science, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  18. Bing Yan

    School of Medical Science, Griffith University, Southport, Australia
    Competing interests
    The authors declare that no competing interests exist.
  19. Bijay Pattnaik

    CSIR Institute of Genomics and Integrative Biology, New Delhi, India
    Competing interests
    The authors declare that no competing interests exist.
  20. Naveen Bhatraju

    CSIR Institute of Genomics and Integrative Biology, New Delhi, India
    Competing interests
    The authors declare that no competing interests exist.
  21. Jaroslav Truksa

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  22. Pavel Stopka

    Department of Zoology, Charles University, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  23. Pavel Hozak

    Institute of Molecular Genetics, Czech Academy of Science, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  24. Alfred Lam

    School of Medicine, Griffith University, Southport, Australia
    Competing interests
    The authors declare that no competing interests exist.
  25. Radislav Sedlacek

    Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  26. Paulo J Oliveira

    Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  27. Mikael Kubista

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  28. Anurag Agrawal

    CSIR Institute of Genomics and Integrative Biology, New Delhi, India
    Competing interests
    The authors declare that no competing interests exist.
  29. Katerina Dvorakova-Hortova

    Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  30. Jakub Rohlena

    Institute of Biotechnology, Czech Academy of Science, Prague, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  31. Michael V Berridge

    Malaghan Institute of Medical Research, Wellington, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  32. Jiri Neuzil

    School of Medical Science, Griffith University, Southport, Australia
    For correspondence
    j.neuzil@griffith.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2478-2460

Funding

Australian Research Council

  • Jiri Neuzil

Czech Science Foundation

  • Jiri Neuzil

BIOCEV European Regional Development Fund

  • Jiri Neuzil

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

Reviewing Editor

  1. Ralph DeBerardinis, UT Southwestern Medical Center, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Czech Republic All animal procedures and experimental protocols were approved by the Local Ethics Committee (Animal Ethics Number 18/2015).

Version history

  1. Received: October 9, 2016
  2. Accepted: February 13, 2017
  3. Accepted Manuscript published: February 14, 2017 (version 1)
  4. Accepted Manuscript updated: February 15, 2017 (version 2)
  5. Version of Record published: March 27, 2017 (version 3)

Copyright

© 2017, Dong 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. Lan-Feng Dong
  2. Jaromira Kovarova
  3. Martina Bajzikova
  4. Ayenachew Bezawork-Geleta
  5. David Svec
  6. Berwini Endaya
  7. Karishma Sachaphibulkij
  8. Ana R Coelho
  9. Natasa Sebkova
  10. Anna Ruzickova
  11. An S Tan
  12. Katarina Kluckova
  13. Kristyna Judasova
  14. Katerina Zamecnikova
  15. Zuzana Rychtarcikova
  16. Vinod Gopalan
  17. Margaryta Sobol
  18. Bing Yan
  19. Bijay Pattnaik
  20. Naveen Bhatraju
  21. Jaroslav Truksa
  22. Pavel Stopka
  23. Pavel Hozak
  24. Alfred Lam
  25. Radislav Sedlacek
  26. Paulo J Oliveira
  27. Mikael Kubista
  28. Anurag Agrawal
  29. Katerina Dvorakova-Hortova
  30. Jakub Rohlena
  31. Michael V Berridge
  32. Jiri Neuzil
(2017)
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells
eLife 6:e22187.
https://doi.org/10.7554/eLife.22187

Share this article

https://doi.org/10.7554/eLife.22187

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