The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models
Jaromı́r Novák, Zuzana Nahácka, Gabriela L. Oliveira, Petra Brisudová, Maria Dubisova, Sarka Dvorakova, Sona Miklovicova, Markéta Dalecká, Verena Puttrich, Lenka Grycová, Silvia Magalhaes Novais, Catarina Mendes Correia, Jennifer Levoux, Ludĕk S̆tĕpánek, Jan Procházka, Dávid Švec, David Pajuelo Reguera, Guillermo López‐Doménech, Renata Zobalová, Radek Sedláček, Mikkel G. Terp, Payam A. Gammage, Zdeněk Lánský, Josef T. Kittler, Paulo J. Oliveira, Henrik J. Ditzel, Michael V. Berridge, Anne‐Marie Rodriguez, Štěpána Boukalová, Jakub Rohlena, Jiřı́ Neužil
Abstract
Recent research has shown that mtDNA-deficient cancer cells (ρ 0 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 KO ) mice markedly delayed tumor formation after grafting ρ 0 cancer cells. Miro1 KO mice with fluorescently labeled mitochondria revealed that this delay was due to hindered mitochondrial transfer from the tumor stromal cells to grafted B16 ρ 0 cells, which impeded recovery of mitochondrial respiration and tumor growth. Miro1 KO 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.