Orchestration of lymphocyte chemotaxis by mitochondrial dynamics.
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.
Campello
Silvia
S
Venetian Institute of Molecular Medicine, Department of Biomedical Science, University of Padua, 35100 Padua, Italy.
Lacalle
Rosa Ana
RA
Bettella
Monica
M
Mañes
Santos
S
Scorrano
Luca
L
Viola
Antonella
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008561:Membrane Fusion / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000235:genetics; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics; D018994:Myosin Light Chains / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D053140:Organelle Shape / Q000187:drug effects; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011753:Pyrones / Q000494:pharmacology; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D002630:Chemotactic Factors; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018994:Myosin Light Chains; D009840:Oligomycins; D011753:Pyrones; C488322:latrunculeic acid; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; C470017:Mfn1 protein, human; C110768:DNM1L protein, human; D034281:Dynamins; D015739:Nocodazole; D000077191:Wortmannin