Miro-1 Links Mitochondria and Microtubule Dynein Motors To Control Lymphocyte Migration and Polarity

Author:

Morlino Giulia12,Barreiro Olga12,Baixauli Francesc12,Robles-Valero Javier3,González-Granado José M.1,Villa-Bellosta Ricardo4,Cuenca Jesús5,Sánchez-Sorzano Carlos O.5,Veiga Esteban67,Martín-Cófreces Noa B.12,Sánchez-Madrid Francisco12

Affiliation:

1. Vascular Biology and Inflammation Department, Centro Nacional Investigaciones Cardiovasculares, Madrid, Spain

2. Servicio de Inmunologia, Instituto Investigación Sanitaria Princesa, Madrid, Spain

3. Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Salamanca, Spain

4. Department of Epidemiology Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain

5. Unidad de Biocomputación, Centro Nacional de Biotecnología (CSIC), Universidad Autónoma de Madrid, Madrid, Spain

6. Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, CSIC, Madrid, Spain

7. Unidad de Investigación, Hospital Santa Cristina, Madrid, Spain

Abstract

ABSTRACT The recruitment of leukocytes to sites of inflammation is crucial for a functional immune response. In the present work, we explored the role of mitochondria in lymphocyte adhesion, polarity, and migration. We show that during adhesion to the activated endothelium under physiological flow conditions, lymphocyte mitochondria redistribute to the adhesion zone together with the microtubule-organizing center (MTOC) in an integrin-dependent manner. Mitochondrial redistribution and efficient lymphocyte adhesion to the endothelium require the function of Miro-1, an adaptor molecule that couples mitochondria to microtubules. Our data demonstrate that Miro-1 associates with the dynein complex. Moreover, mitochondria accumulate around the MTOC in response to the chemokine CXCL12/SDF-1α; this redistribution is regulated by Miro-1. CXCL12-dependent cell polarization and migration are reduced in Miro-1-silenced cells, due to impaired myosin II activation at the cell uropod and diminished actin polymerization. These data point to a key role of Miro-1 in the control of lymphocyte adhesion and migration through the regulation of mitochondrial redistribution.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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