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.

Genomics Research Centre Institute of Health and Biomedical Innovation Queensland University of Technology Kelvin Grove QLD 4059 Australia

Institute of Biotechnology Academy of Sciences of the Czech Republic Prague 142 20 Czech Republic

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague 142 20 Czech Republic

Malaghan Institute of Medical Research P O Box 7060 Wellington 6242 New Zealand

School of Medical Science Griffith University Southport QLD 4222 Australia

School of Medical Science Griffith University Southport QLD 4222 Australia; Institute of Biotechnology Academy of Sciences of the Czech Republic Prague 142 20 Czech Republic

Komentář v

Cell Metab. 2015 Jan 6;21(1):11-2. doi: 10.1016/j.cmet.2014.12.013. PubMed

Komentář v

Nat Rev Cancer. 2015 Feb;15(2):70. doi: 10.1038/nrc3901. PubMed

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