The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse

During antigen‐specific T‐cell activation, mitochondria mobilize towards the vicinity of the immune synapse. We show here that the mitochondrial fission factor dynamin‐related protein 1 (Drp1) docks at mitochondria, regulating their positioning and activity near the actin‐rich ring of the peripheral supramolecular activation cluster (pSMAC) of the immune synapse. Mitochondrial redistribution in response to T‐cell receptor engagement was abolished by Drp1 silencing, expression of the phosphomimetic mutant Drp1S637D and the Drp1‐specific inhibitor mdivi‐1. Moreover, Drp1 knockdown enhanced mitochondrial depolarization and T‐cell receptor signal strength, but decreased myosin phosphorylation, ATP production and T‐cell receptor assembly at the central supramolecular activation cluster (cSMAC). Our results indicate that Drp1‐dependent mitochondrial positioning and activity controls T‐cell activation by fuelling central supramolecular activation cluster assembly at the immune synapse. During antigen presentation, T cells relocalize organelles, adhesion and signalling components to the immunological synapse (IS). This study shows that the localization of mitochondria to the IS is regulated by the mitochondrial fission factor Drp1 and that this is important for T‐cell activation.