title: The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse.
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.
authors.affiliation: Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Baixauli
authors.forename: Noa B
authors.initials: NB
authors.lastname: Martín-Cófreces
authors.forename: Giulia
authors.initials: G
authors.lastname: Morlino
authors.forename: Yolanda R
authors.initials: YR
authors.lastname: Carrasco
authors.forename: Carmen
authors.initials: C
authors.lastname: Calabia-Linares
authors.forename: Esteban
authors.initials: E
authors.lastname: Veiga
authors.forename: Juan M
authors.initials: JM
authors.lastname: Serrador
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D054992:Immunological Synapses / Q000502:physiology* / Q000648:ultrastructure*; D008214:Lymphocytes / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D050505:Mutant Proteins; D011948:Receptors, Antigen, T-Cell; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins