Editors' ChoiceImmunology

Mitochondrial Positioning in T Cells

Science Signaling  12 Apr 2011:
Vol. 4, Issue 168, pp. ec99
DOI: 10.1126/scisignal.4168ec99

Mitochondria are central to many cellular processes because they produce energy in the form of adenosine triphosphate (ATP) and they buffer intracellular Ca2+. The functions of mitochondria are regulated by altering the balance between their fusion and fission, processes mediated by dynamin-related guanosine triphosphatases (GTPases), and by the positioning of mitochondria within the cell (see commentary by Junker and Hoth). The recruitment of mitochondria to synapses in neurons and immune cells is critical for supplying sufficient local concentrations of ATP to drive the various processes that occur at these sites. Baixauli et al. investigated the regulation of mitochondrial positioning near the immune synapse in T cells that were activated in vitro by antigen-presenting cells or plate-bound antibodies. Stimulation of the T cell receptor (TCR) resulted in the recruitment of mitochondria near the peripheral supramolecular complex (pSMAC) of the immune synapse, which surrounds the central cluster of TCRs (the cSMAC). Inhibition or knockdown of the mitochondrial fission factor Drp1, which localized to mitochondria after T cell stimulation, inhibited the translocation of mitochondria to the pSMAC in response to TCR activation. Silencing of Drp1 also inhibited the clustering of TCRs at the cSMAC, which resulted in increased numbers of TCR microclusters at the pSMAC. Mitochondrial membrane potential and ATP production were compromised in T cells in which Drp1 was knocked down, as was myosin activation, which is required for the clustering of TCRs at the cSMAC. When TCRs reach the cSMAC, their signaling is inhibited. Because of the increased numbers of TCR clusters at the pSMAC, signaling downstream of the TCR was enhanced in Drp1-silenced T cells compared with that in control cells. Together, these data suggest that Drp1-mediated regulation of mitochondrial positioning controls formation of the immune synapse and regulates the strength of TCR signaling.

F. Baixauli, N. B. Martín-Cófreces, G. Morlino, Y. R. Carrasco, C. Calabia-Linares, E. Veiga, J. M. Serrador, F. Sánchez-Madrid, The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse. EMBO J. 30, 1238–1250 (2011). [PubMed]

C. Junker, M. Hoth, Immune synapses: Mitochondrial morphology matters. EMBO J. 30, 1187–1189 (2011). [PubMed]