Mitochondrial Genome Acquisition Restores Respiratory Function and Tumorigenic Potential of Cancer Cells without Mitochondrial DNA
Affiliations
- Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand
Affiliations
- Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand
Affiliations
- School of Medical Science, Griffith University, Southport, QLD 4222, Australia
Affiliations
- School of Medical Science, Griffith University, Southport, QLD 4222, Australia
Affiliations
- School of Medical Science, Griffith University, Southport, QLD 4222, Australia
Affiliations
- School of Medical Science, Griffith University, Southport, QLD 4222, Australia
Affiliations
- Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- School of Medical Science, Griffith University, Southport, QLD 4222, Australia
Affiliations
- School of Medical Science, Griffith University, Southport, QLD 4222, Australia
Affiliations
- Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
Affiliations
- Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- School of Medical Science, Griffith University, Southport, QLD 4222, Australia
Affiliations
- Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
Affiliations
- Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand
Affiliations
- Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
Affiliations
- Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
Affiliations
- 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
Correspondence
- Corresponding author
Affiliations
- 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
Correspondence
- Corresponding author
Affiliations
- Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand
Correspondence
- Corresponding author
Affiliations
- Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand
Correspondence
- Corresponding author
Article Info
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Highlights
- •Tumor cells lacking mtDNA form tumors only after acquiring host mtDNA
- •Tumor microenvironment instructs stepwise recovery of respiration
- •Recovery of mitochondrial function aligns with efficient tumor formation
- •Functional respirasome and complex II assembly occur in metastatic cells
Summary
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.