Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA
Open accessAbstract
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.
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Targeted depletion of mitochondrial DNA reduces the tumorigenic potential of cancer cell lines in vitro and in vivo.
“targeted depletion of mitochondrial DNA reduces the tumorigenic potential of cancer cell lines in vitro and in vivo”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Tan et al., 2015
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- Authors
- Tan, A. S., Baty, J. W., Dong, L.-F., Bezawork-Geleta, A., Endaya, B., Goodwin, J., Bajzikova, M., Kovarova, J., Peterka, M., Yan, B., Pesdar, E. A., Sobol, M., Filimonenko, A., Stuart, S., Vondrusova, M., Kluckova, K., Sachaphibulkij, K., Rohlena, J., Hozak, P., Truksa, J., Eccles, D., Haupt, L. M., Griffiths, L. R., Neuzil, J., & Berridge, M. V.
- Affiliations
- Malaghan Institute of Medical Research (NZ)
- Griffith University (AU)
- Czech Academy of Sciences (CZ)
- Queensland University of Technology (AU)
- Corresponding author
- Berridge, Michael V.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 21
- Issue
- 1
- Pages
- 81-94
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2030637794
- Cited by
- 785
- References
- 64
- Citations by year
- 2026: 60 · 2025: 60 · 2024: 65 · 2023: 73 · 2022: 70 · 2021: 63 · 2020: 92 · 2019: 73 · 2018: 62 · 2017: 62 · 2016: 68 · 2015: 35 · 2014: 1
- FWCI
- 32.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- ASEP (publishedVersion)
- QUT ePrints (Queensland University of Technology) (acceptedVersion)
- Griffith Research Online (submittedVersion)
- Funders
- Breast Cancer Research Trust
- Cancer Society of New Zealand
- Grantová Agentura České Republiky
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- tumor microenvironment, mitochondrial respiration, circulating tumor cells, lung metastasis, cancer stem cells, mitochondrial DNA damage, tumor plasticity
- MeSH terms
- Animals, Citrate (si)-Synthase, DNA, Mitochondrial, Energy Metabolism, Lung Neoplasms, Melanoma, Experimental, Mice, Inbred BALB C, Mice, Inbred C57BL, Mitochondria, NADH Dehydrogenase, RNA, Messenger, Transplantation, Homologous, Mice, SCID, Mice, Inbred NOD, Reactive Oxygen Species, Electron Transport Chain Complex Proteins, Cell Line, Tumor, Cell Proliferation, Mice
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