Tunneling nanotubes mediate mitochondrial homeostasis in cancer
Abstract
Tumor progression is driven by cancer cells’ ability to establish a cellular network through tunneling nanotube-like connections (TNTs), which enable mitochondrial exchange both within the tumor cells and with the tumor microenvironment (TME). However, the functional consequences of mitochondrial transfer between tumor and non-tumor cells, and its occurrence in vivo, remain poorly understood. Here we show bidirectional mitochondrial transfer between Glioblastoma (GBM) cells and non-tumoral astrocytes (AS). We report that transfer of damaged mitochondria from GBM cells to AS is associated with activation of mitophagy in recipient cells, while astrocyte-derived mitochondria to GBM cells correlates with changes in mitochondrial activity and metabolic readouts. Furthermore, intravital subcellular microscopy (ISMic) in a live animal model allows the visualization of TNT connections with characteristics similar to those observed in vitro and supported TNT-mediated mitochondrial transfer in vivo. These findings reveal a potential mechanism of tumor adaptation and highlight TNTs as promising therapeutic targets.
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BibTeX
@article{saenzdesantamaria2026tunneling,
title = {{Tunneling nanotubes mediate mitochondrial homeostasis in cancer}},
author = {Ines Saenz-De-Santa-Maria and Anna Pepe and Jean-Yves Tinevez and Christel Brou and Iakov Vitrenko and Thomas Cokelaer and Elizabeth Cohen-Jonathan Moyal and Roberto Weigert and Chiara Zurzolo},
journal = {Nature Communications},
year = {2026},
month = jun,
doi = {10.1038/s41467-026-76619-9},
url = {https://pasteur.hal.science/pasteur-05669755v2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tunneling nanotubes mediate mitochondrial homeostasis in cancer
AU - Ines Saenz-De-Santa-Maria
AU - Anna Pepe
AU - Jean-Yves Tinevez
AU - Christel Brou
AU - Iakov Vitrenko
AU - Thomas Cokelaer
AU - Elizabeth Cohen-Jonathan Moyal
AU - Roberto Weigert
AU - Chiara Zurzolo
PY - 2026
DA - 2026/06/15
JO - Nature Communications
DO - 10.1038/s41467-026-76619-9
UR - https://pasteur.hal.science/pasteur-05669755v2
AB - Tumor progression is driven by cancer cells’ ability to establish a cellular network through tunneling nanotube-like connections (TNTs), which enable mitochondrial exchange both within the tumor cells and with the tumor microenvironment (TME). However, the functional consequences of mitochondrial transfer between tumor and non-tumor cells, and its occurrence in vivo, remain poorly understood. Here we show bidirectional mitochondrial transfer between Glioblastoma (GBM) cells and non-tumoral astrocytes (AS). We report that transfer of damaged mitochondria from GBM cells to AS is associated with activation of mitophagy in recipient cells, while astrocyte-derived mitochondria to GBM cells correlates with changes in mitochondrial activity and metabolic readouts. Furthermore, intravital subcellular microscopy (ISMic) in a live animal model allows the visualization of TNT connections with characteristics similar to those observed in vitro and supported TNT-mediated mitochondrial transfer in vivo. These findings reveal a potential mechanism of tumor adaptation and highlight TNTs as promising therapeutic targets.
SN - 2041-1723
SN - 2041-1723
ER -