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PNAS 104 (36): 14418-14423

Copyright © 2007 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

T cell activation requires mitochondrial translocation to the immunological synapse

Ariel Quintana*, Christian Schwindling, Anna S. Wenning, Ute Becherer, Jens Rettig, Eva C. Schwarz, and Markus Hoth

Department of Physiology, Saarland University, Gebäude 58/59, D-66421 Homburg, Germany

Edited by Arthur Weiss, University of California School of Medicine, San Francisco, CA, and approved July 30, 2007

Received for publication April 7, 2007.

Abstract: T helper (Th) cell activation is required for the adaptive immune response. Formation of the immunological synapse (IS) between Th cells and antigen-presenting cells is essential for Th cell activation. IS formation induces the polarization and redistribution of many signaling molecules; however, very little is known about organelle redistribution during IS formation in Th cells. We show that formation of the IS induced cytoskeleton-dependent mitochondrial redistribution to the immediate vicinity of the IS. Using total internal reflection microscopy, we found that upon stimulation, the distance between the IS and mitochondria was decreased to values <200 nm. Consequently, mitochondria close to the IS took up more Ca2+ than the ones farther away from the IS. The redistribution of mitochondria to the IS was necessary to maintain Ca2+ influx across the plasma membrane and Ca2+-dependent Th cell activation. Our results suggest that mitochondria are part of the signaling complex at the IS and that their localization close to the IS is required for Th cell activation.

Key Words: calcium • lymphocyte • mitochondria

Author contributions: A.Q., E.C.S., and M.H. designed research; A.Q., C.S., A.S.W., and U.B. performed research; A.Q., C.S., A.S.W., U.B., J.R., E.C.S., and M.H. analyzed data; and A.Q., J.R., E.C.S., and M.H. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0703126104/DC1.

*To whom correspondence should be addressed. E-mail: ptaqgo{at}uks.eu

© 2007 by The National Academy of Sciences of the USA

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