Mitochondrial transfer via tunneling nanotubes (TNT-mediated mitochondrial transfer)

Mitochondrial transfer via tunneling nanotubes (TNTs) is a specialized form of intercellular communication involving the translocation of functional mitochondria through thin, actin-rich cytoplasmic bridges (Rustom et al., 2004, Science). This biological process serves as a mechanism for metabolic rescue, allowing healthy donor cells, such as mesenchymal stem cells, to restore the bioenergetic capacity of stressed or damaged recipient cells (Spees et al., 2006, PNAS). The transport is actively regulated by molecular motors and adaptor proteins, most notably the Rho-GTPase Miro1 (RHOT1), which facilitates the movement of mitochondria along the TNT cytoskeleton (Ahmad et al., 2014, EMBO J). In disease contexts, this transfer can be double-edged; while it promotes tissue regeneration in ischemic or inflammatory conditions, it is also hijacked by cancer cells to acquire metabolic advantages and evade chemotherapy-induced apoptosis (Pasquier et al., 2013, J Transl Med). Furthermore, TNTs have been implicated in the spread of neurodegenerative pathologies by facilitating the transfer of misfolded proteins alongside mitochondria (Zhu et al., 2015, FEBS Lett). Current therapeutic research explores the pharmacological modulation of TNT formation and mitochondrial trafficking, using agents like CD38 inhibitors or actin-polymerization modifiers to control these intercellular exchanges (Sinclair et al., 2016, Blood).

Other names

Intercellular mitochondrial transferTNT-mediated organelle transportMitochondrial trafficking via TNTsMitochondrial donation

Modulation of actin polymerization, Miro1-mediated mitochondrial transport, and CD38-cADPR signaling pathways to regulate the formation of tunneling nanotubes and the subsequent translocation of mitochondria between cells.