The Journal of Experimental Medicine
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Published online December 4, 2006
doi:10.1084/jem.20061877
The Journal of Experimental Medicine, Vol. 203, No. 13, 2879-2886
The Rockefeller University Press, 0022-1007 $30.00
© 2006 Campello et al.
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ARTICLE

 Orchestration of lymphocyte chemotaxis by mitochondrial dynamics

Silvia Campello1, Rosa Ana Lacalle2, Monica Bettella1, Santos Mañes2, Luca Scorrano3, and Antonella Viola1,4

1 Venetian Institute of Molecular Medicine, Department of Biomedical Science, University of Padua, 35100 Padua, Italy
2 Department of Immunology and Oncology, Centro Nacional de Biotecnologia, 28049 Madrid, Spain
3 Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy
4 Istituto Clinico Humanitas, 20089 Rozzano (MI), Italy

CORRESPONDENCE Antonella Viola: antonella.viola{at}unipd.it

Lymphocyte traffic is required to maintain homeostasis and perform appropriate immunological reactions. To migrate into inflamed tissues, lymphocytes must acquire spatial and functional asymmetries. Mitochondria are highly dynamic organelles that distribute in the cytoplasm to meet specific cellular needs, but whether this is essential to lymphocyte functions is unknown. We show that mitochondria specifically concentrate at the uropod during lymphocyte migration by a process involving rearrangements of their shape. Mitochondrial fission facilitates relocation of the organelles and promotes lymphocyte chemotaxis, whereas mitochondrial fusion inhibits both processes. Our data substantiate a new role for mitochondrial dynamics and suggest that mitochondria redistribution is required to regulate the motor of migrating cells.

Abbreviations used: AKTPH-GFP, pleckstrin homology domain of AKT fused to GFP; CCL, CC chemokine ligand; CXCL, CXC chemokine ligand; dHL-60, differentiated HL-60; Drp1, dynamin-related protein 1; fMLP, N-formyl-Met-Leu-Phe; Mfn, mitofusin; MLC, myosin light chain; MTOC, microtubule organizing center; mtRFP and mtYFP, mitochondrially targeted red fluorescent protein and yellow fluorescent protein, respectively; PB T cell, peripheral blood T cell; PI3K, phosphoinositide 3–kinase; PTx, Pertussis toxin.


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