Intercellular mitochondrial transfer via tunnelling nanotubes (TNTs) has been shown to influence cellular bioenergetics and function in tumours. Now in Cell, Baldwin et al. exploit this concept to increase mitochondrial function in CD8+ T cells, preventing T cell exhaustion and boosting antitumour efficacy.

Using RNA sequencing, the authors aimed to identify the mechanisms of mitochondrial transfer. Talin 2 (TLN2) and LPXN were among the few commonly upregulated genes in human and mouse Mito+ cells compared with their respective Mito− cells. Because talins have a role in integrin activation, membrane dynamics and cellular outgrowth, the authors reasoned that TLN2 could be important for promoting TNT formation. Individual knockout of TLN2 in BMSCs and CD8+ T cells impaired mitochondrial transfer but had more pronounced effects when knocked out in BMSCs. Moreover, pharmacological disruption of TNT formation with L-788,123 prevented mitochondrial transfer when pre-treating BMSCs, but not CD8+ T cells. This suggests that BMSCs are the initiating cells of mitochondrial transfer.