The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
39792553
DOI
10.1016/j.celrep.2024.115154
PII: S2211-1247(24)01505-5
Knihovny.cz E-resources
- Keywords
- CP: Cancer, CP: Cell biology, Miro1, RHOT1, cancer, horizontal transfer of mitochondria, melanoma, mitochondria, tunneling nanotubes,
- MeSH
- Humans MeSH
- Melanoma, Experimental * pathology metabolism genetics MeSH
- Mesenchymal Stem Cells metabolism MeSH
- Microtubules metabolism MeSH
- Mitochondrial Proteins metabolism genetics MeSH
- Mitochondria * metabolism MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout * MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- rho GTP-Binding Proteins metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Miro-1 protein, mouse MeSH Browser
- Mitochondrial Proteins MeSH
- rho GTP-Binding Proteins MeSH
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.
Cancer Research UK Scotland Institute Glasgow G61 1BD UK
Faculty of Science Charles University 128 00 Prague Czech Republic
Institute of Biotechnology Czech Academy of Sciences 252 50 Prague West Czech Republic
Institute of Molecular Medicine University of Southern Denmark 5000 Odense Denmark
Malaghan Institute of Medical Research Wellington 6012 New Zealand
Sorbonne University Institute of Biology Paris Seine 75005 Paris France
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