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Elife. 2017 Feb 15;6. pii: e22187. doi: 10.7554/eLife.22187.

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

Author information

1
School of Medical Science, Griffith University, Southport, Australia.
2
Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
3
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
4
Department of Zoology, Faculty of Science, Charles University, Prague, Czech Republic.
5
Malaghan Institute of Medical Research, Wellington, New Zealand.
6
Zittau/Goerlitz University of Applied Sciences, Zittau, Germany.
7
Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic.
8
School of Medicine, Griffith University, Southport, Australia.
9
Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
10
CSIR Institute of Genomics and Integrative Biology, New Delhi, India.
11
TATAA Biocenter, Gothenburg, Sweden.

Abstract

Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0 cells) is linked to the acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether the 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.

KEYWORDS:

cancer biology; mitochondrial transfer; mouse; respiration recovery; tumour growth

PMID:
28195532
PMCID:
PMC5367896
DOI:
10.7554/eLife.22187
[Indexed for MEDLINE]
Free PMC Article

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