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Immunological Synapse Formation Induces Mitochondrial Clustering and Mitophagy in Dendritic Cells.

Accepted version
Peer-reviewed

Type

Article

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Authors

Gómez-Cabañas, Laura 
López-Cotarelo, Pilar 
Criado-García, Olga 
Murphy, Michael P 
Boya, Patricia 

Abstract

The immunological synapse (IS) is a superstructure formed during T cell activation at the zone of contact between T cells and dendritic cells (DCs). The IS includes specific molecular components in the T cell and DCs sides that may result in different functionality. Most of the studies on the IS have focused on the T cell side of this structure and, in contrast, the information available on the IS of DCs is sparse. Autophagy is a cellular process involved in the clearance of damaged proteins and organelles via lysosomal degradation. Mitophagy is the selective autophagy of damaged mitochondria. In this study, it is shown that IS formation induces clustering of mitochondria in the IS of DCs and partial depolarization of these organelles. At the IS of the DCs also accumulate autophagy and mitophagy markers, even when the kinase complex mTORC1, an inhibitor of the autophagy, is active. Together the results presented indicate that IS formation induces local clustering of mitochondria and mitophagy, which could be a homeostatic mechanism to control the quality of mitochondria in this region. The data underline the complexity of the regulatory mechanisms operating in the IS of DCs.

Description

Keywords

Animals, Dendritic Cells, Immunological Synapses, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, Mitochondria, Mitophagy

Journal Title

Journal of Immunology

Conference Name

Journal ISSN

1550-6606
1550-6606

Volume Title

202

Publisher

American Association of Immunologists
Sponsorship
Medical Research Council (MC_UU_00015/3)
Wellcome Trust (110159/Z/15/Z)
Medical Research Council (MC_U105663142)
This work was supported by Grants SAF-2014-53151-R (Ministerio de Economı´a y Competitividad), SAF2017-83306-R (Ministerio de Ciencia, Innovacio´n y Universidades), RD08/0075 (Red de Inflamacio´n y Enfermedades Reuma´ticas [Redes Tema´ticas de Investigacio´n Cooperativa en Salud Program/Instituto de Salud Carlos III]), and S2010/BMD-2350 (Consejerı´a de Educacio´n y Empleo from Comunidad de Madrid [Raphyme]) (to J.L.R.-F.). L.G.-C. and P.L.-C were supported by fellowships Formacio´n del Profesorado Universitario and Formacio´n de Personal Investigador, conferred by the Ministerio de Educacio´n y Ciencia and Ministerio de Economı´a y Competitividad, respectively. M.P.M. was supported by the Medical Research Council UK (MC_U105663142) and a Wellcome Trust Investigator Award (110159/Z/15/Z).