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

• DOI: 10.7554/elife.22187
• Publication Date: 2017-02-14T13:00:09Z
• Authors: Lan-Feng Dong; Jaromira Kovarova; Martina Bajzikova; Ayenachew Bezawor...; David Svec; Berwini Endaya; Karishma Sachaphi...; Ana R Coelho; Natasa Sebkova; Anna Ruzickova; An S Tan; Katarina Kluckova; Kristyna Judasova; Katerina Zamecnikova; Zuzana Rychtarcikova; Vinod Gopalan; Ladislav Andera; Margarita Sobol; Bing Yan; Bijay Pattnaik; Naveen Bhatraju; Jaroslav Truksa; Pavel Stopka; Pavel Hozak; Alfred K Lam; Radislav Sedlacek; Paulo J Oliveira; Mikael Kubista; Anurag Agrawal; Katerina Dvorakov...; Jakub Rohlena; Michael V Berridge; Jiri Neuzil
• Keywords: 2800 Neuroscience; 0301 basic medicine; 570; Biomedical and clinical sciences; 1300 Biochemistry; Gene Transfer, Horizontal; QH301-705.5; Biochemistry and cell biology not elsewhere classified; Science; Cell Respiration; 610; Genetics and Molecular Biology; DNA, Mitochondrial; respiration recovery; 03 medical and health sciences; Cell Line, Tumor; Animals; Biology (General); Melanoma; Cancer Biology; General Immunology and Microbiology; General Neuroscience; tumour growth; Q; mitochondrial transfer; R; Health sciences; 2400 Immunology and Microbiology; General Medicine; 3. Good health; Mice, Inbred C57BL; Biological sciences; Disease Models, Animal; Biochemistry and cell biology; General Biochemistry; Medicine

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