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.

CNC Center for Neuroscience and Cell Biology University of Coimbra Cantanhede Portugal

CSIR Institute of Genomics and Integrative Biology New Delhi India

Department of Zoology Faculty of Science Charles University Prague Czech Republic

Faculty of Pharmacy Charles University Hradec Kralove Czech Republic

Institute of Biotechnology Czech Academy of Sciences Prague Czech Republic

Institute of Molecular Genetics Czech Academy of Sciences Prague Czech Republic

Malaghan Institute of Medical Research Wellington New Zealand

School of Medical Science Griffith University Southport Australia

School of Medicine Griffith University Southport Australia

TATAA Biocenter Gothenburg Sweden

Zittau Goerlitz University of Applied Sciences Zittau Germany

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