This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schubert, A. Articles by Grimm, S. Search for Related Content PubMed PubMed Citation Articles by Schubert, A. Articles by Grimm, S.

Cyclophilin D, a Component of the Permeability Transition-Pore, Is an Apoptosis Repressor

Max-Planck-Institute for Biochemistry, Martinsried, Germany

The permeability transition (PT)-pore is an important proapoptotic protein complex in mitochondria. Although it is activated by many signals for apoptosis induction, the role of its various subunits in cell death induction has remained largely unknown. We found that of its components, only the voltage-dependent anion channel in the outer mitochondrial membrane and the adenine nucleotide translocator-1 (ANT-1), a PT-pore subunit of the inner membrane, are apoptosis inducers. We also report that ANT-1’s direct interactor, cyclophilin D, can specifically repress ANT-1-induced apoptosis. In addition, cotransfection experiments revealed that for a diverse range of apoptosis inducers, cyclophilin D shows the same repression profile as the compound bongkrekic acid, a specific inhibitor of the PT-pore. This activity seems to be independent of its chaperone activity, the only known function of cyclophilin D to date. Importantly, cyclophilin D is specifically up-regulated in human tumors of the breast, ovary, and uterus, suggesting that inhibition of the PT-pore via up-regulation of cyclophilin D plays a role in tumorigenesis.

This article has been cited by other articles:

				R. A. Eliseev, J. Malecki, T. Lester, Y. Zhang, J. Humphrey, and T. E. Gunter Cyclophilin D Interacts with Bcl2 and Exerts an Anti-apoptotic Effect J. Biol. Chem., April 10, 2009; 284(15): 9692 - 9699. [Abstract] [Full Text] [PDF]

				L. Argaud, O. Gateau-Roesch, L. Augeul, E. Couture-Lepetit, J. Loufouat, L. Gomez, D. Robert, and M. Ovize Increased mitochondrial calcium coexists with decreased reperfusion injury in postconditioned (but not preconditioned) hearts Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H386 - H391. [Abstract] [Full Text] [PDF]

				G. Kroemer, L. Galluzzi, and C. Brenner Mitochondrial Membrane Permeabilization in Cell Death Physiol Rev, January 1, 2007; 87(1): 99 - 163. [Abstract] [Full Text] [PDF]

				T. Hang, Z. Huang, S. Jiang, J. Gong, C. Wang, D. Xie, and H. Ren Apoptosis in pressure overload-induced cardiac hypertrophy is mediated, in part, by adenine nucleotide translocator-1. Ann. Clin. Lab. Sci., December 1, 2006; 36(1): 88 - 95. [Abstract] [Full Text] [PDF]

				M. Le Bras, A. Borgne-Sanchez, Z. Touat, O. S. El Dein, A. Deniaud, E. Maillier, G. Lecellier, D. Rebouillat, C. Lemaire, G. Kroemer, et al. Chemosensitization by knockdown of adenine nucleotide translocase-2. Cancer Res., September 15, 2006; 66(18): 9143 - 9152. [Abstract] [Full Text] [PDF]

				R. J. Braun, H. Zischka, F. Madeo, T. Eisenberg, S. Wissing, S. Buttner, S. M. Engelhardt, D. Buringer, and M. Ueffing Crucial Mitochondrial Impairment upon CDC48 Mutation in Apoptotic Yeast J. Biol. Chem., September 1, 2006; 281(35): 25757 - 25767. [Abstract] [Full Text] [PDF]

				K. Machida, Y. Ohta, and H. Osada Suppression of Apoptosis by Cyclophilin D via Stabilization of Hexokinase II Mitochondrial Binding in Cancer Cells J. Biol. Chem., May 19, 2006; 281(20): 14314 - 14320. [Abstract] [Full Text] [PDF]

				V. Temkin, Q. Huang, H. Liu, H. Osada, and R. M. Pope Inhibition of ADP/ATP Exchange in Receptor-Interacting Protein-Mediated Necrosis. Mol. Cell. Biol., March 1, 2006; 26(6): 2215 - 2225. [Abstract] [Full Text] [PDF]

				M. Potts, S. M. Slaughter, F.-U. Hunneke, J. F. Garst, and R. F. Helm Desiccation Tolerance of Prokaryotes: Application of Principles to Human Cells Integr. Comp. Biol., November 1, 2005; 45(5): 800 - 809. [Abstract] [Full Text] [PDF]

				A. C. Schinzel, O. Takeuchi, Z. Huang, J. K. Fisher, Z. Zhou, J. Rubens, C. Hetz, N. N. Danial, M. A. Moskowitz, and S. J. Korsmeyer Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia PNAS, August 23, 2005; 102(34): 12005 - 12010. [Abstract] [Full Text] [PDF]

				E. Yehuda-Shnaidman, B. Kalderon, and J. Bar-Tana Modulation of Mitochondrial Transition Pore Components by Thyroid Hormone Endocrinology, May 1, 2005; 146(5): 2462 - 2472. [Abstract] [Full Text] [PDF]

				S. Gu, Z. Liu, S. Pan, Z. Jiang, H. Lu, O. Amit, E. M. Bradbury, C.-A. A. Hu, and X. Chen Global Investigation of p53-induced Apoptosis Through Quantitative Proteomic Profiling Using Comparative Amino Acid-coded Tagging Mol. Cell. Proteomics, October 1, 2004; 3(10): 998 - 1008. [Abstract] [Full Text] [PDF]

				M. Zamora, C. Merono, O. Vinas, and T. Mampel Recruitment of NF-{kappa}B into Mitochondria Is Involved in Adenine Nucleotide Translocase 1 (ANT1)-induced Apoptosis J. Biol. Chem., September 10, 2004; 279(37): 38415 - 38423. [Abstract] [Full Text] [PDF]