title: Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA.
abstract: 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.
authors.affiliation: Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand.
authors.forename: An S
authors.initials: AS
authors.lastname: Tan
authors.affiliation: Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand.
authors.forename: James W
authors.initials: JW
authors.lastname: Baty
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Lan-Feng
authors.initials: LF
authors.lastname: Dong
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Ayenachew
authors.initials: A
authors.lastname: Bezawork-Geleta
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Berwini
authors.initials: B
authors.lastname: Endaya
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: Goodwin
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Bajzikova
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Jaromira
authors.initials: J
authors.lastname: Kovarova
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Peterka
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Elham Alizadeh
authors.initials: EA
authors.lastname: Pesdar
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Margarita
authors.initials: M
authors.lastname: Sobol
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Anatolyj
authors.initials: A
authors.lastname: Filimonenko
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.
authors.forename: Shani
authors.initials: S
authors.lastname: Stuart
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Vondrusova
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kluckova
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
authors.forename: Karishma
authors.initials: K
authors.lastname: Sachaphibulkij
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Rohlena
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hozak
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Truksa
authors.affiliation: Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Eccles
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
authors.affiliation: 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. Electronic address: j.neuzil@griffith.edu.au.
authors.forename: Jiri
authors.initials: J
authors.lastname: Neuzil
authors.affiliation: Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand. Electronic address: mberridge@malaghan.org.nz.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Berridge
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009245:NADH Dehydrogenase; D002950:Citrate (si)-Synthase