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

0474268 - BTÚ 2018 RIV US eng J - Journal Article
Dong, L. F. - Kovářová, Jaromíra - Bajziková, Martina - Bezawork-Geleta, A. - Švec, David - Endaya, B. - Sachaphibulkij, K. - Coelho, Ana R. - Šebková, Nataša - Ruzickova, A. - Tan, A.S. - Klučková, Katarína - Judasová, Kateřina - Zamecnikova, K. - Rychtarčíková, Zuzana - Gopalan, V. - Anděra, Ladislav - Sobol, Margaryta - Yan, B. - Pattnaik, B. - Bhatraju, N. - Truksa, Jaroslav - Stopka, P. - Hozák, Pavel - Lam, A. K. - Sedláček, Radislav - Oliveira, P.J. - Kubista, Mikael - Agrawal, A. - Dvořáková-Hortová, Kateřina - Rohlena, Jakub - Berridge, M.V. - Neužil, Jiří
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondria! DNA-deficient cancer cells.
eLife. Roč. 6, 15 Febr 2017 (2017), č. článku e22187. ISSN 2050-084X. E-ISSN 2050-084X
R&D Projects: GA ČR(CZ) GA16-12816S; GA MŠMT(CZ) LM2011032; GA ČR(CZ) GA16-22823S; GA ČR GA17-20904S; GA MŠMT LO1419; GA ČR(CZ) GA16-12719S; GA ČR GA15-02203S; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:86652036 ; RVO:68378050
Keywords : SUPPORTING ASPARTATE BIOSYNTHESIS * ELECTRON-TRANSPORT CHAIN * OXIDATIVE-PHOSPHORYLATION
OECD category: Biochemistry and molecular biology; Health-related biotechnology (UMG-J)
Impact factor: 7.616, year: 2017

Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (rho(0) 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 B16 rho(0) mouse melanoma cells into syngeneic C576116N(su9DsRed2) 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 B16 rho(0) 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.
Permanent Link: http://hdl.handle.net/11104/0271401