4.8 Article

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

Journal

EMBO JOURNAL
Volume 30, Issue 7, Pages 1238-1250

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2011.25

Keywords

cell signalling; fission factor; immune synapse; mitochondria; T-cell receptor

Funding

  1. Spanish Ministry of Science and Innovation [SAF2008-02635]
  2. Instituto Carlos III [Red RECAVA RD06/0014-0030]
  3. Comunidad de Madrid [INSINET 0159/2006]
  4. Fundacion CNIC
  5. European Union
  6. Pro-CNIC Foundation
  7. [PI070356]

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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. The EMBO Journal (2011) 30, 1238-1250. doi: 10.1038/emboj.2011.25; Published online 15 February 2011

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