Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA
Tan, An S., Baty, James W., Dong, Lan-Feng, Bezawork-Geleta, Ayenachew, Endaya, Berwini, Goodwin, Jacob, Bajzikova, Martina, Kovarova, Jaromira, Peterka, Martin, Yan, Bing, Pesdar, Elham Alizadeh, Sobol, Margarita, Filimonenko, Anatolyj, Stuart, Shani, Vondrusova, Magdalena, Kluckova, Katarina, Sachaphibulkij, Karishma, Rohlena, Jakub, Hozak, Pavel, Truksa, Jaroslav, Eccles, David, Haupt, Larisa M., Griffiths, Lyn R., Neuzil, Jiri, & Berridge, Michael V. (2015) Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metabolism, 21(1), pp. 81-94.
We report that tumor cells devoid of their mitochondrial genome (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 supercomplexes 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 a novel pathophysiological process for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.
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|Item Type:||Journal Article|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2015 Elsevier Inc.|
|Copyright Statement:||NOTICE: this is the author’s version of a work that was accepted for publication in Cell Metabolism. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cell Metabolism, Volume 21, Issue 1, 6 January 2015, DOI: 10.1016/j.cmet.2014.12.003|
|Deposited On:||22 Jan 2015 00:14|
|Last Modified:||11 Jan 2016 00:32|
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