Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells
Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0 cells) 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 m...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/22187 |
| _version_ | 1811227972466638848 |
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| author | Lan-Feng Dong Jaromira Kovarova Martina Bajzikova Ayenachew Bezawork-Geleta David Svec Berwini Endaya Karishma Sachaphibulkij Ana R Coelho Natasa Sebkova Anna Ruzickova An S Tan Katarina Kluckova Kristyna Judasova Katerina Zamecnikova Zuzana Rychtarcikova Vinod Gopalan Ladislav Andera Margarita Sobol Bing Yan Bijay Pattnaik Naveen Bhatraju Jaroslav Truksa Pavel Stopka Pavel Hozak Alfred K Lam Radislav Sedlacek Paulo J Oliveira Mikael Kubista Anurag Agrawal Katerina Dvorakova-Hortova Jakub Rohlena Michael V Berridge Jiri Neuzil |
| author_facet | Lan-Feng Dong Jaromira Kovarova Martina Bajzikova Ayenachew Bezawork-Geleta David Svec Berwini Endaya Karishma Sachaphibulkij Ana R Coelho Natasa Sebkova Anna Ruzickova An S Tan Katarina Kluckova Kristyna Judasova Katerina Zamecnikova Zuzana Rychtarcikova Vinod Gopalan Ladislav Andera Margarita Sobol Bing Yan Bijay Pattnaik Naveen Bhatraju Jaroslav Truksa Pavel Stopka Pavel Hozak Alfred K Lam Radislav Sedlacek Paulo J Oliveira Mikael Kubista Anurag Agrawal Katerina Dvorakova-Hortova Jakub Rohlena Michael V Berridge Jiri Neuzil |
| author_sort | Lan-Feng Dong |
| collection | DOAJ |
| description | Recently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0 cells) 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 B16ρ0 mouse melanoma cells into syngeneic C57BL/6Nsu9-DsRed2 mice 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 B16ρ0 cells 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. |
| first_indexed | 2024-04-12T09:50:41Z |
| format | Article |
| id | doaj.art-4285105d6a3d4ae5a57e35604fc4c03d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:50:41Z |
| publishDate | 2017-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4285105d6a3d4ae5a57e35604fc4c03d2022-12-22T03:37:50ZengeLife Sciences Publications LtdeLife2050-084X2017-02-01610.7554/eLife.22187Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cellsLan-Feng Dong0Jaromira Kovarova1Martina Bajzikova2Ayenachew Bezawork-Geleta3David Svec4Berwini Endaya5Karishma Sachaphibulkij6Ana R Coelho7Natasa Sebkova8Anna Ruzickova9An S Tan10Katarina Kluckova11Kristyna Judasova12Katerina Zamecnikova13Zuzana Rychtarcikova14Vinod Gopalan15Ladislav Andera16Margarita Sobol17Bing Yan18Bijay Pattnaik19Naveen Bhatraju20Jaroslav Truksa21Pavel Stopka22Pavel Hozak23Alfred K Lam24Radislav Sedlacek25Paulo J Oliveira26Mikael Kubista27Anurag Agrawal28Katerina Dvorakova-Hortova29Jakub Rohlena30Michael V Berridge31Jiri Neuzil32https://orcid.org/0000-0002-2478-2460School of Medical Science, Griffith University, Southport, AustraliaInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicSchool of Medical Science, Griffith University, Southport, AustraliaInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicSchool of Medical Science, Griffith University, Southport, AustraliaSchool of Medical Science, Griffith University, Southport, AustraliaInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, PortugalInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic; Department of Zoology, Faculty of Science, Charles University, Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicMalaghan Institute of Medical Research, Wellington, New ZealandInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic; Zittau/Goerlitz University of Applied Sciences, Zittau, GermanyInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic; Faculty of Pharmacy, Charles University, Hradec Kralove, Czech RepublicSchool of Medical Science, Griffith University, Southport, Australia; School of Medicine, Griffith University, Southport, AustraliaInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech RepublicSchool of Medical Science, Griffith University, Southport, AustraliaCSIR Institute of Genomics and Integrative Biology, New Delhi, IndiaCSIR Institute of Genomics and Integrative Biology, New Delhi, IndiaInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicDepartment of Zoology, Faculty of Science, Charles University, Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech RepublicSchool of Medicine, Griffith University, Southport, AustraliaInstitute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech RepublicCNC-Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, PortugalInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic; TATAA Biocenter, Gothenburg, SwedenCSIR Institute of Genomics and Integrative Biology, New Delhi, IndiaInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic; Department of Zoology, Faculty of Science, Charles University, Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicMalaghan Institute of Medical Research, Wellington, New ZealandSchool of Medical Science, Griffith University, Southport, Australia; Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech RepublicRecently, we showed that generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0 cells) 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 B16ρ0 mouse melanoma cells into syngeneic C57BL/6Nsu9-DsRed2 mice 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 B16ρ0 cells 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.https://elifesciences.org/articles/22187mitochondrial transferrespiration recoverytumour growth |
| spellingShingle | Lan-Feng Dong Jaromira Kovarova Martina Bajzikova Ayenachew Bezawork-Geleta David Svec Berwini Endaya Karishma Sachaphibulkij Ana R Coelho Natasa Sebkova Anna Ruzickova An S Tan Katarina Kluckova Kristyna Judasova Katerina Zamecnikova Zuzana Rychtarcikova Vinod Gopalan Ladislav Andera Margarita Sobol Bing Yan Bijay Pattnaik Naveen Bhatraju Jaroslav Truksa Pavel Stopka Pavel Hozak Alfred K Lam Radislav Sedlacek Paulo J Oliveira Mikael Kubista Anurag Agrawal Katerina Dvorakova-Hortova Jakub Rohlena Michael V Berridge Jiri Neuzil Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells eLife mitochondrial transfer respiration recovery tumour growth |
| title | Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
| title_full | Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
| title_fullStr | Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
| title_full_unstemmed | Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
| title_short | Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
| title_sort | horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial dna deficient cancer cells |
| topic | mitochondrial transfer respiration recovery tumour growth |
| url | https://elifesciences.org/articles/22187 |
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