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The mitochondrial localization of RelB and NFATx in immature T cells


In order to exert their activity, transcription factors must be transported to the nucleus. Certain transcription factors have also been found on mitochondria. Here, the localization of RelB and NFATx in the mitochondrial fractions of normal thymocytes and thymic lymphoma cells is shown for the first time. CREB was only found in the nucleus, while p50 (NFκB) was found in both the nucleus and the cytoplasm, but outside the mitochondria. The translocation of transcription factors to the mitochondria is differentially regulated. Unlike RelB, which is always present in the mitochondrial fraction, NFATx appeared on the mitochondria in cells treated with ionomycin together with an immunosuppressant and inhibitor of calcineurin (FK506). This data reveals that the mitochondrial localization of some transcription factors is precisely controlled by a calcium signal sensitive to FK506 in T cells.



activator protein 1


cAMP response element-binding protein


enhanced chemiluminescence


foetal calf serum


glucocorticoid receptor


60-kDA heat-shock protein


c-Jun N-terminal kinase


nuclear factor of activated T cells 3


nuclear factor κB


phosphate-buffered saline


polyvinylidene difluoride


mitogenactivated protein kinase p38


sodium dodecyl sulphate


SDS-polyacrylamide gel electrophoresis


Tris buffer solution


T-cell receptor


  1. Cammarota, M., Paratcha, G., Bevilaqua, L.R., Levi de Stein, M., Lopez, M., Pellegrino de Iraldi, A., Izquierdo, I. and Medina, J.H. Cyclic AMPresponsive element binding protein in brain mitochondria. J. Neurochem. 72 (1999) 2272–2277.

    PubMed  Article  CAS  Google Scholar 

  2. Yang, S.H., Liu, R., Perez, E.J., Wen, Y., Stevens, S.M., Valencia, T., Brun-Zinkernagel, A.M., Prokai, L., Will, Y., Dykens, J., Koulen, P. and Simpkins, J.W. Mitochondrial localization of estrogen receptor β. Proc. Natl. Acad. Sci. USA 101 (2004) 4130–4135.

    PubMed  Article  CAS  Google Scholar 

  3. Ogita, K., Okuda, H., Kitano, M., Fujinami, Y., Ozaki, K. and Yoneda, Y. Localization of activator protein-1 complex with DNA binding activity in mitochondria of murine brain after in vivo treatment with kainite. J. Neurosci. 22 (2002) 2561–2570.

    PubMed  CAS  Google Scholar 

  4. Cogswell, P.C., Kashatus, D.F., Keifer, J.A., Cuttridge, D.G., Reuther, J.Y., Bristow, C., Roy, S., Nicholson, D.W. and Baldwin, A.S. NFκB and IκBα are found in the mitochondria. J. Biol. Chem. 278 (2003) 2963–2968.

    PubMed  Article  CAS  Google Scholar 

  5. Li, H., Kolluri, S.K., Gu, J., Dawson, M.I., Cao, X., Hobbs, P.D., Lin, B., Chen, G.Q., Lu, J.S., Lin, F., Xie, Z., Fontana, J.A., Reed, J.C. and Zhang, X.K. Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science 289 (2000) 1159–1164.

    PubMed  Article  CAS  Google Scholar 

  6. Sionov, R.V, Cohen, O., Kfir, S., Zilberman, Y. and Yefenof, E. Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis. J. Exp. Med. 203 (2006) 189–201.

    PubMed  Article  CAS  Google Scholar 

  7. Marchenko, N.D., Zaika, A. and Moll, U.M. Death signal-induced localization of p53 protein to mitochondria. J. Biol. Chem. 275 (2000) 16202–16212.

    PubMed  Article  CAS  Google Scholar 

  8. Barrett, L.E., Van Bockstaele, E.J., Sul, J.Y., Takano, H., Haydon, P.G. and Eberwine, J.H. Elk-1 associates with the mitochondrial permeability transition pore complex in neurons. Proc. Natl. Acad. Sci. USA 103 (2006) 5155–5160.

    PubMed  Article  CAS  Google Scholar 

  9. Feske, S., Okamura, H., Hogan, P.G. and Rao, A. Ca2+/calcineurin signalling in cells of the immune system. Biochem. Biophys. Res. Commun. 311 (2003) 1117–1132.

    PubMed  Article  CAS  Google Scholar 

  10. Guerin, S., Baron, M.L., Valero, R., Herrant, M., Auberger, P. and Naquet P. RelB reduces thymocyte apoptosis and regulates terminal thymocyte maturation. Eur. J. Immunol. 32 (2002) 1–9.

    PubMed  Article  CAS  Google Scholar 

  11. Oukka, M., Ho, I.C., de la Brousse, F.C., Hoey, T., Grusby, M.J. and Glimcher, L.H. The transcription factor NFAT4 is involved in the generation and survival of T cells. Immunity 9 (1998) 295–304.

    PubMed  Article  CAS  Google Scholar 

  12. Woronicz, J.D., Lina, A., Calnan, B.J., Szychowski, S., Cheng, L. and Winoto, A. Regulation of the Nur77 orphan steroid receptor in activationinduced apoptosis. Mol. Cell Biol. 15 (1995) 6364–6376.

    PubMed  CAS  Google Scholar 

  13. Matsuda, S., Shibasaki, F., Takehana, K., Mori, H., Nishida, E. and Koyasu, S. Two distinct action mechanisms of immunophilin-ligand complexes for the blockade of T-cell activation. EMBO Rep. 1 (2000) 428–434.

    PubMed  Article  CAS  Google Scholar 

  14. Woo, J., Ildstad, S.T. and Thomson, A.W. FK506 inhibits the differentiation of developing thymocytes but not negative selection of T cell receptor V beta 5+ and V beta 11+ T lymphocytes in vivo. Transpl. Immunol. 2 (1994) 11–21.

    PubMed  Article  CAS  Google Scholar 

  15. Kalas, W., Matuszyk, J., Ziolo, E. and Strzadala, L. FK506 restores sensitivity of thymic lymphomas to calcium-mediated apoptosis and the inducible expression of Fas ligand. Anticancer Res. 23 (2B) (2003) 1613–1617.

    PubMed  CAS  Google Scholar 

  16. Stasik, I., Rapak, A., Kalas, W., Ziolo, E. and Strzadala, L. Ionomycin-induced apoptosis of thymocytes is independent of Nur77 NBRE or NurRE binding, but is accompanied by Nur77 mitochondrial targeting. Biochim. Biophys. Acta. 1773 (2007) 1483–1490.

    PubMed  Article  CAS  Google Scholar 

  17. Strzadala, L., Miazek, A., Matuszyk, J. and Kisielow, P. Role of thymic selection in the development of thymic lymphomas in TCR transgenic mice. Int. Immunol. 9 (1997) 127–138.

    PubMed  Article  CAS  Google Scholar 

  18. Bottero, V., Rossi, F., Samson, M., Mari, M., Hofman, P. and Peyron, J.F. IκB-α, the NF-κB inhibitory subunit, interacts with ANT, the mitochondrial ATP/ADP translocator. J. Biol. Chem. 276 (2001) 21317–21324.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Leon Strządała.

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Stasik, I., Rapak, A., Zioło, E. et al. The mitochondrial localization of RelB and NFATx in immature T cells. Cell Mol Biol Lett 13, 493–501 (2008).

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Key words

  • Mitochondrial translocation
  • Transcription factors
  • NFATx
  • RelB
  • FK506
  • Thymocytes
  • Thymic lymphoma