title: Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells.
abstract: Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0cells) is linked to the acquisition of the host mtDNA. However, the mechanism of mtDNA movement between cells remains unresolved. To determine whether the transfer of mtDNA involves whole mitochondria, we injected B16ρ0mouse melanoma cells into syngeneic C57BL/6Nsu9-DsRed2mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration. Additionally, knockdown of key mitochondrial complex I (NDUFV1) and complex II (SDHC) subunits by shRNA in B16ρ0cells abolished or significantly retarded their ability to form tumours. Collectively, these results show that intact mitochondria with their mtDNA payload are transferred in the developing tumour, and provide functional evidence for an essential role of oxidative phosphorylation in cancer.
authors.affiliation: School of Medical Science, Griffith University, Southport, Australia.
authors.forename: Lan-Feng
authors.initials: LF
authors.lastname: Dong
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Jaromira
authors.initials: J
authors.lastname: Kovarova
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Bajzikova
authors.affiliation: School of Medical Science, Griffith University, Southport, Australia.
authors.forename: Ayenachew
authors.initials: A
authors.lastname: Bezawork-Geleta
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Svec
authors.affiliation: School of Medical Science, Griffith University, Southport, Australia.
authors.forename: Berwini
authors.initials: B
authors.lastname: Endaya
authors.affiliation: School of Medical Science, Griffith University, Southport, Australia.
authors.forename: Karishma
authors.initials: K
authors.lastname: Sachaphibulkij
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.|CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Coelho
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.|Department of Zoology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Natasa
authors.initials: N
authors.lastname: Sebkova
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Ruzickova
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: An S
authors.initials: AS
authors.lastname: Tan
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kluckova
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Judasova
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.|Zittau/Goerlitz University of Applied Sciences, Zittau, Germany.
authors.forename: Katerina
authors.initials: K
authors.lastname: Zamecnikova
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.|Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Rychtarcikova
authors.affiliation: School of Medical Science, Griffith University, Southport, Australia.|School of Medicine, Griffith University, Southport, Australia.
authors.forename: Vinod
authors.initials: V
authors.lastname: Gopalan
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Andera
authors.affiliation: Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Margarita
authors.initials: M
authors.lastname: Sobol
authors.affiliation: School of Medical Science, Griffith University, Southport, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: CSIR Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Bijay
authors.initials: B
authors.lastname: Pattnaik
authors.affiliation: CSIR Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Bhatraju
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Truksa
authors.affiliation: Department of Zoology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Stopka
authors.affiliation: Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hozak
authors.affiliation: School of Medicine, Griffith University, Southport, Australia.
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Lam
authors.affiliation: Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Radislav
authors.initials: R
authors.lastname: Sedlacek
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.|TATAA Biocenter, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Kubista
authors.affiliation: CSIR Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.|Department of Zoology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorakova-Hortova
authors.affiliation: Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Rohlena
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Berridge
authors.affiliation: School of Medical Science, Griffith University, Southport, Australia.|Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Jiri
authors.identifier: 0000-0002-2478-2460
authors.initials: J
authors.lastname: Neuzil
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019069:Cell Respiration; D004272:DNA, Mitochondrial / Q000235:genetics*; D004195:Disease Models, Animal; D022761:Gene Transfer, Horizontal; D008545:Melanoma / Q000473:pathology*; D008810:Mice, Inbred C57BL
chemical_list: D004272:DNA, Mitochondrial
keywords: cancer biology; mitochondrial transfer; mouse; respiration recovery; tumour growth