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EMBO J. 2011 Apr 6;30(7):1238-50. doi: 10.1038/emboj.2011.25. Epub 2011 Feb 15.

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

Author information

1
Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.

Abstract

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.

PMID:
21326213
PMCID:
PMC3094108
DOI:
10.1038/emboj.2011.25
[Indexed for MEDLINE]
Free PMC Article

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