Vascular Biology and Inflammation Department, Centro Nacional Investigaciones Cardiovasculares, Madrid, Spain.
Mol Cell Biol. 2014 Apr;34(8):1412-26. doi: 10.1128/MCB.01177-13. Epub 2014 Feb 3.
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.
白细胞向炎症部位的募集对于功能性免疫反应至关重要。在本研究中，我们探讨了线粒体在淋巴细胞黏附、极性和迁移中的作用。我们发现，在生理流动条件下黏附于激活的血管内皮细胞时，淋巴细胞的线粒体与微管组织中心（MTOC）一起，以整合素依赖性方式重新分布到黏附区域。线粒体的重新分布以及淋巴细胞与内皮细胞的有效黏附需要衔接分子 Miro-1 的功能，该分子将线粒体与微管偶联。我们的数据表明，Miro-1 与动力蛋白复合物相关联。此外，线粒体在外源趋化因子 CXCL12/SDF-1α 的刺激下在 MTOC 周围聚集；这种重分布受 Miro-1 调控。由于细胞尾足处肌球蛋白 II 的激活受损以及肌动蛋白聚合减少，Miro-1 沉默的细胞中细胞的极化和迁移减少。这些数据表明，Miro-1 通过调节线粒体的重新分布，在控制淋巴细胞黏附和迁移方面发挥关键作用。
