The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models

Summary: Recent research has shown that mtDNA-deficient cancer cells (ρ0 cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this p...

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Main Authors: Jaromir Novak, Zuzana Nahacka, Gabriela L. Oliveira, Petra Brisudova, Maria Dubisova, Sarka Dvorakova, Sona Miklovicova, Marketa Dalecka, Verena Puttrich, Lenka Grycova, Silvia Magalhaes-Novais, Catarina Mendes Correia, Jennifer Levoux, Ludek Stepanek, Jan Prochazka, David Svec, David Pajuelo Reguera, Guillermo Lopez-Domenech, Renata Zobalova, Radek Sedlacek, Mikkel G. Terp, Payam A. Gammage, Zdenek Lansky, Josef Kittler, Paulo J. Oliveira, Henrik J. Ditzel, Michael V. Berridge, Anne-Marie Rodriguez, Stepana Boukalova, Jakub Rohlena, Jiri Neuzil
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724015055
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author Jaromir Novak
Zuzana Nahacka
Gabriela L. Oliveira
Petra Brisudova
Maria Dubisova
Sarka Dvorakova
Sona Miklovicova
Marketa Dalecka
Verena Puttrich
Lenka Grycova
Silvia Magalhaes-Novais
Catarina Mendes Correia
Jennifer Levoux
Ludek Stepanek
Jan Prochazka
David Svec
David Pajuelo Reguera
Guillermo Lopez-Domenech
Renata Zobalova
Radek Sedlacek
Mikkel G. Terp
Payam A. Gammage
Zdenek Lansky
Josef Kittler
Paulo J. Oliveira
Henrik J. Ditzel
Michael V. Berridge
Anne-Marie Rodriguez
Stepana Boukalova
Jakub Rohlena
Jiri Neuzil
author_facet Jaromir Novak
Zuzana Nahacka
Gabriela L. Oliveira
Petra Brisudova
Maria Dubisova
Sarka Dvorakova
Sona Miklovicova
Marketa Dalecka
Verena Puttrich
Lenka Grycova
Silvia Magalhaes-Novais
Catarina Mendes Correia
Jennifer Levoux
Ludek Stepanek
Jan Prochazka
David Svec
David Pajuelo Reguera
Guillermo Lopez-Domenech
Renata Zobalova
Radek Sedlacek
Mikkel G. Terp
Payam A. Gammage
Zdenek Lansky
Josef Kittler
Paulo J. Oliveira
Henrik J. Ditzel
Michael V. Berridge
Anne-Marie Rodriguez
Stepana Boukalova
Jakub Rohlena
Jiri Neuzil
author_sort Jaromir Novak
collection DOAJ
description Summary: Recent research has shown that mtDNA-deficient cancer cells (ρ0 cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1KO) mice markedly delayed tumor formation after grafting ρ0 cancer cells. Miro1KO mice with fluorescently labeled mitochondria revealed that this delay was due to hindered mitochondrial transfer from the tumor stromal cells to grafted B16 ρ0 cells, which impeded recovery of mitochondrial respiration and tumor growth. Miro1KO led to the perinuclear accumulation of mitochondria and impaired mobility of the mitochondrial network. In vitro experiments revealed decreased association of mitochondria with microtubules, compromising mitochondrial transfer via tunneling nanotubes (TNTs) in mesenchymal stromal cells. Here we show the role of Miro1 in horizontal mitochondrial transfer in mouse melanoma models in vivo and its involvement with TNTs.
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spelling doaj-art-85fb633a244e4576a0814bf2863768862025-01-11T06:41:12ZengElsevierCell Reports2211-12472025-01-01441115154The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma modelsJaromir Novak0Zuzana Nahacka1Gabriela L. Oliveira2Petra Brisudova3Maria Dubisova4Sarka Dvorakova5Sona Miklovicova6Marketa Dalecka7Verena Puttrich8Lenka Grycova9Silvia Magalhaes-Novais10Catarina Mendes Correia11Jennifer Levoux12Ludek Stepanek13Jan Prochazka14David Svec15David Pajuelo Reguera16Guillermo Lopez-Domenech17Renata Zobalova18Radek Sedlacek19Mikkel G. Terp20Payam A. Gammage21Zdenek Lansky22Josef Kittler23Paulo J. Oliveira24Henrik J. Ditzel25Michael V. Berridge26Anne-Marie Rodriguez27Stepana Boukalova28Jakub Rohlena29Jiri Neuzil30Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Corresponding authorInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; NC-UC, Center for Neuroscience and Cell Biology, University of Coimbra, 3060-197 Cantanhede, Portugal; CIBB, Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3060-197 Cantanhede, Portugal; Institute for Interdisciplinary Research, Doctoral Program in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, 3060-197 Cantanhede, PortugalInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech RepublicFaculty of Science, Charles University, 128 00 Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Czech Center for Phenogenomic, Institute of Molecular Genetics, Czech Academy of Sciences, 252 50 Vestec, Czech RepublicCancer Research UK Scotland Institute, Glasgow G61 1BD, UKSorbonne University, Institute of Biology Paris-Seine, 75005 Paris, FranceCzech Center for Phenogenomic, Institute of Molecular Genetics, Czech Academy of Sciences, 252 50 Vestec, Czech RepublicCzech Center for Phenogenomic, Institute of Molecular Genetics, Czech Academy of Sciences, 252 50 Vestec, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech RepublicCzech Center for Phenogenomic, Institute of Molecular Genetics, Czech Academy of Sciences, 252 50 Vestec, Czech RepublicDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech RepublicCzech Center for Phenogenomic, Institute of Molecular Genetics, Czech Academy of Sciences, 252 50 Vestec, Czech RepublicInstitute of Molecular Medicine, University of Southern Denmark, 5000 Odense, DenmarkCancer Research UK Scotland Institute, Glasgow G61 1BD, UK; School of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UKInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech RepublicDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKNC-UC, Center for Neuroscience and Cell Biology, University of Coimbra, 3060-197 Cantanhede, Portugal; CIBB, Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3060-197 Cantanhede, PortugalInstitute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; Department of Oncology, Odense University Hospital, 5000 Odense, DenmarkMalaghan Institute of Medical Research, Wellington 6012, New ZealandSorbonne University, Institute of Biology Paris-Seine, 75005 Paris, France; University Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, FranceInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech RepublicInstitute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech Republic; School of Pharmacy and Medical Science, Griffith University, Southport, QLD 4222, Australia; 1st Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic; Corresponding authorSummary: Recent research has shown that mtDNA-deficient cancer cells (ρ0 cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1KO) mice markedly delayed tumor formation after grafting ρ0 cancer cells. Miro1KO mice with fluorescently labeled mitochondria revealed that this delay was due to hindered mitochondrial transfer from the tumor stromal cells to grafted B16 ρ0 cells, which impeded recovery of mitochondrial respiration and tumor growth. Miro1KO led to the perinuclear accumulation of mitochondria and impaired mobility of the mitochondrial network. In vitro experiments revealed decreased association of mitochondria with microtubules, compromising mitochondrial transfer via tunneling nanotubes (TNTs) in mesenchymal stromal cells. Here we show the role of Miro1 in horizontal mitochondrial transfer in mouse melanoma models in vivo and its involvement with TNTs.http://www.sciencedirect.com/science/article/pii/S2211124724015055CP: CancerCP: Cell biology
spellingShingle Jaromir Novak
Zuzana Nahacka
Gabriela L. Oliveira
Petra Brisudova
Maria Dubisova
Sarka Dvorakova
Sona Miklovicova
Marketa Dalecka
Verena Puttrich
Lenka Grycova
Silvia Magalhaes-Novais
Catarina Mendes Correia
Jennifer Levoux
Ludek Stepanek
Jan Prochazka
David Svec
David Pajuelo Reguera
Guillermo Lopez-Domenech
Renata Zobalova
Radek Sedlacek
Mikkel G. Terp
Payam A. Gammage
Zdenek Lansky
Josef Kittler
Paulo J. Oliveira
Henrik J. Ditzel
Michael V. Berridge
Anne-Marie Rodriguez
Stepana Boukalova
Jakub Rohlena
Jiri Neuzil
The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
Cell Reports
CP: Cancer
CP: Cell biology
title The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
title_full The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
title_fullStr The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
title_full_unstemmed The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
title_short The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
title_sort adaptor protein miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
topic CP: Cancer
CP: Cell biology
url http://www.sciencedirect.com/science/article/pii/S2211124724015055
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