Mitochondrial Genome Acquisition Restores Respiratory Function and Tumorigenic Potential of Cancer Cells without Mitochondrial DNA

0440852 - BTÚ 2015 RIV US eng J - Journal Article
Tan, A.S. - Dong, L.F. - Bezawork-Geleta, A. - Endaya, B. - Goodwin, J. - Bajziková, Martina - Kovářová, Jaromíra - Peterka, Martin - Yan, B. - Alizadeh Pesdar, E. - Sobol, Margaryta - Filimonenko, Anatolij - Stuart, S. - Vondrusová, Magdaléna - Klučková, Katarína - Sachaphibulkij, K. - Rohlena, Jakub - Hozák, Pavel - Truksa, Jaroslav - Eccles, D. - Haupt, D. - Griffiths, L.R. - Neužil, Jiří - Berridge, M.V.
Mitochondrial Genome Acquisition Restores Respiratory Function and Tumorigenic Potential of Cancer Cells without Mitochondrial DNA.
Cell Metabolism. Roč. 21, č. 1 (2015), s. 81-94. ISSN 1550-4131. E-ISSN 1932-7420
R&D Projects: GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR(CZ) GAP301/10/1937; GA ČR GA15-02203S; GA ČR GAP305/12/1708; GA ČR GAP301/12/1851
Institutional support: RVO:86652036 ; RVO:68378050
Keywords : ELECTRON-TRANSPORT CHAIN * MAMMALIAN MITOCHONDRIA * TUNNELING NANOTUBES
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 17.303, year: 2015

We report that tumor cells without mitochondrial DNA (mtDNA) show delayed tumor growth, and that tumor formation is associated with acquisition of mtDNA from host cells. This leads to partial recovery of mitochondrial function in cells derived from primary tumors grown from cells without mtDNA and a shorter lag in tumor growth. Cell lines from circulating tumor cells showed further recovery of mitochondrial respiration and an intermediate lag to tumor growth, while cells from lung metastases exhibited full restoration of respiratory function and no lag in tumor growth. Stepwise assembly of mitochondrial respiratory (super)complexes was correlated with acquisition of respiratory function. Our findings indicate horizontal transfer of mtDNA from host cells in the tumor microenvironment to tumor cells with compromised respiratory function to re-establish respiration and tumor-initiating efficacy. These results suggest pathophysiological processes for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.
Permanent Link: http://hdl.handle.net/11104/0243952