The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
Recent research has shown that mtDNA-deficient cancer cells (ρ<sup>0</sup> 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 (Miro1<sup>KO</sup>) mice markedly delayed tumor formation after grafting ρ<sup>0</sup> cancer cells. Miro1<sup>KO</sup> mice with fluorescently labeled mitochondria revealed that this delay was due to hindered mitochondrial transfer from the tumor stromal cells to grafted B16 ρ<sup>0</sup> cells, which impeded recovery of mitochondrial respiration and tumor growth. Miro1<sup>KO</sup> 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.
Authors
- Mikkel G. Terp (ORCID: https://orcid.org/0000-0002-4468-6900)
- Dávid Švec (ORCID: https://orcid.org/0000-0002-3893-6803)
- Zdeněk Lánský (ORCID: https://orcid.org/0000-0001-8474-053X)
- Maria Dubisova (ORCID: https://orcid.org/0009-0001-6086-5052)
- Zuzana Nahácka (ORCID: https://orcid.org/0000-0003-0477-2764)
- Michael V. Berridge (ORCID: https://orcid.org/0000-0003-2619-7473)
- Henrik J. Ditzel (ORCID: https://orcid.org/0000-0003-3927-5135)
- Silvia Magalhaes Novais (ORCID: https://orcid.org/0000-0002-9053-4676)
- Radek Sedláček (ORCID: https://orcid.org/0000-0001-8468-5921)
- David Pajuelo Reguera (ORCID: https://orcid.org/0000-0002-7715-9402)
- Lenka Grycová (ORCID: https://orcid.org/0000-0002-6476-3627)
- Jaromı́r Novák (ORCID: https://orcid.org/0000-0001-5851-9399)
- Josef T. Kittler (ORCID: https://orcid.org/0000-0002-3437-9456)
- Petra Brisudová (ORCID: https://orcid.org/0009-0001-9751-9356)
- Verena Puttrich
- Luděk Štěpánek (ORCID: https://orcid.org/0000-0003-2160-5706)
- Jiřı́ Neužil (ORCID: https://orcid.org/0000-0002-2478-2460)
- Jakub Rohlena (ORCID: https://orcid.org/0000-0001-5427-6502)
- Markéta Dalecká (ORCID: https://orcid.org/0000-0003-4366-0255)
- Anne‐Marie Rodriguez (ORCID: https://orcid.org/0000-0001-5557-8975)
- Sarka Dvorakova
- Štěpána Boukalová (ORCID: https://orcid.org/0000-0002-6478-4604)
- Payam A. Gammage (ORCID: https://orcid.org/0000-0003-1968-1726)
- Guillermo López‐Doménech (ORCID: https://orcid.org/0000-0002-3114-2082)
- Renata Zobalová (ORCID: https://orcid.org/0000-0002-9097-4700)
- Gabriela L. Oliveira
- Paulo J. Oliveira (ORCID: https://orcid.org/0000-0002-5201-9948)
- Catarina Mendes Correia (ORCID: https://orcid.org/0000-0002-8562-0086)
- Jan Procházka
- Sona Miklovicova
- Jennifer Levoux
Institutions
- Griffith University (AU)
- Inserm (FR)
- University of Southern Denmark (DK)
- Université Paris-Est Créteil (FR)
- Malaghan Institute of Medical Research (NZ)
- Czech Academy of Sciences (CZ)
- Charles University (CZ)
- Paris-Est Sup (FR)
- Cancer Research UK (GB)
- Odense University Hospital (DK)
- Sorbonne Université (FR)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Institut de Biologie Paris-Seine (FR)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- Cell2B (Portugal) (PT)
- Institut Mondor de Recherche Biomédicale (FR)
- University College London (GB)
- University of Coimbra (PT)
- University of Glasgow (GB)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.115154
- Citations
- 16
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 12.90
Funders
- Univerzita Karlova v Praze
- Grantová Agentura, Univerzita Karlova
- Cancer Research UK
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Grantová Agentura České Republiky
- Ministerstvo Zdravotnictví Ceské Republiky
- Akademie Věd České Republiky
- Fundação para a Ciência e a Tecnologia
- European Regional Development Fund