Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells
- Griffith University, Australia
- Czech Academy of Sciences, Czech Republic
- Czech Academy of Science, Czech Republic
- Malaghan Institute of Medical Research, New Zealand
- CSIR Institute of Genomics and Integrative Biology, India
- Charles University, Czech Republic
- University of Coimbra, Portugal
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.
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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.
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).
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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Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells
eLife 6:e22187.
https://doi.org/10.7554/eLife.22187
