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

Novak, J; Nahacka, Z; Oliveira, GL; Brisudova, P; Dubisova, M; Dvorakova, S; Miklovicova, S; ... Neuzil, J; + view all (2025) The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models. Cell Reports , 44 (1) , Article 115154. 10.1016/j.celrep.2024.115154. Green open access

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Abstract

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.

Type: Article
Title: The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2024.115154
Publisher version: https://doi.org/10.1016/j.celrep.2024.115154
Language: English
Additional information: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: CP: Cancer, CP: Cell biology, Miro1, RHOT1, cancer, horizontal transfer of mitochondria, melanoma, mitochondria, tunneling nanotubes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10204351
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