Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108138 https://doi.org/10.7554/eLife.22187 |
Resumo: | 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. |
id |
RCAP_ff978ac9a030989bfa5fd1ff5aaf36a1 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/108138 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cellscancer biology; mitochondrial transfer; mouse; respiration recovery; tumour growthAnimalsCell Line, TumorCell RespirationDNA, MitochondrialDisease Models, AnimalMelanomaMice, Inbred C57BLGene Transfer, HorizontalRecently, 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.eLife Sciences Publications2017-02-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108138http://hdl.handle.net/10316/108138https://doi.org/10.7554/eLife.22187eng2050-084XDong, Lan-FengKovarova, JaromiraBajzikova, MartinaBezawork-Geleta, AyenachewSvec, DavidEndaya, BerwiniSachaphibulkij, KarishmaCoelho, Ana R.Sebkova, NatasaRuzickova, AnnaTan, An SKluckova, KatarinaJudasova, KristynaZamecnikova, KaterinaRychtarcikova, ZuzanaGopalan, VinodAndera, LadislavSobol, MargaritaYan, BingPattnaik, BijayBhatraju, NaveenTruksa, JaroslavStopka, PavelHozak, PavelLam, Alfred K.Sedlacek, RadislavOliveira, Paulo J.Kubista, MikaelAgrawal, AnuragDvorakova-Hortova, KaterinaRohlena, JakubBerridge, Michael V.Neuzil, Jiriinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-12T18:24:57Zoai:estudogeral.uc.pt:10316/108138Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:26.030118Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
title |
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
spellingShingle |
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells Dong, Lan-Feng cancer biology; mitochondrial transfer; mouse; respiration recovery; tumour growth Animals Cell Line, Tumor Cell Respiration DNA, Mitochondrial Disease Models, Animal Melanoma Mice, Inbred C57BL Gene Transfer, Horizontal |
title_short |
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_sort |
Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells |
author |
Dong, Lan-Feng |
author_facet |
Dong, Lan-Feng Kovarova, Jaromira Bajzikova, Martina Bezawork-Geleta, Ayenachew Svec, David Endaya, Berwini Sachaphibulkij, Karishma Coelho, Ana R. Sebkova, Natasa Ruzickova, Anna Tan, An S Kluckova, Katarina Judasova, Kristyna Zamecnikova, Katerina Rychtarcikova, Zuzana Gopalan, Vinod Andera, Ladislav Sobol, Margarita Yan, Bing Pattnaik, Bijay Bhatraju, Naveen Truksa, Jaroslav Stopka, Pavel Hozak, Pavel Lam, Alfred K. Sedlacek, Radislav Oliveira, Paulo J. Kubista, Mikael Agrawal, Anurag Dvorakova-Hortova, Katerina Rohlena, Jakub Berridge, Michael V. Neuzil, Jiri |
author_role |
author |
author2 |
Kovarova, Jaromira Bajzikova, Martina Bezawork-Geleta, Ayenachew Svec, David Endaya, Berwini Sachaphibulkij, Karishma Coelho, Ana R. Sebkova, Natasa Ruzickova, Anna Tan, An S Kluckova, Katarina Judasova, Kristyna Zamecnikova, Katerina Rychtarcikova, Zuzana Gopalan, Vinod Andera, Ladislav Sobol, Margarita Yan, Bing Pattnaik, Bijay Bhatraju, Naveen Truksa, Jaroslav Stopka, Pavel Hozak, Pavel Lam, Alfred K. Sedlacek, Radislav Oliveira, Paulo J. Kubista, Mikael Agrawal, Anurag Dvorakova-Hortova, Katerina Rohlena, Jakub Berridge, Michael V. Neuzil, Jiri |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Dong, Lan-Feng Kovarova, Jaromira Bajzikova, Martina Bezawork-Geleta, Ayenachew Svec, David Endaya, Berwini Sachaphibulkij, Karishma Coelho, Ana R. Sebkova, Natasa Ruzickova, Anna Tan, An S Kluckova, Katarina Judasova, Kristyna Zamecnikova, Katerina Rychtarcikova, Zuzana Gopalan, Vinod Andera, Ladislav Sobol, Margarita Yan, Bing Pattnaik, Bijay Bhatraju, Naveen Truksa, Jaroslav Stopka, Pavel Hozak, Pavel Lam, Alfred K. Sedlacek, Radislav Oliveira, Paulo J. Kubista, Mikael Agrawal, Anurag Dvorakova-Hortova, Katerina Rohlena, Jakub Berridge, Michael V. Neuzil, Jiri |
dc.subject.por.fl_str_mv |
cancer biology; mitochondrial transfer; mouse; respiration recovery; tumour growth Animals Cell Line, Tumor Cell Respiration DNA, Mitochondrial Disease Models, Animal Melanoma Mice, Inbred C57BL Gene Transfer, Horizontal |
topic |
cancer biology; mitochondrial transfer; mouse; respiration recovery; tumour growth Animals Cell Line, Tumor Cell Respiration DNA, Mitochondrial Disease Models, Animal Melanoma Mice, Inbred C57BL Gene Transfer, Horizontal |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-02-15 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/108138 http://hdl.handle.net/10316/108138 https://doi.org/10.7554/eLife.22187 |
url |
http://hdl.handle.net/10316/108138 https://doi.org/10.7554/eLife.22187 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2050-084X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
eLife Sciences Publications |
publisher.none.fl_str_mv |
eLife Sciences Publications |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799134129141317632 |