This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Belzacq, A.-S. Articles by Brenner, C. Search for Related Content PubMed PubMed Citation Articles by Belzacq, A.-S. Articles by Brenner, C.

Apoptosis Induction by the Photosensitizer Verteporfin: Identification of Mitochondrial Adenine Nucleotide Translocator as a Critical Target¹

Centre National de la Recherche Scientifique, UMR 6022, Université de Technologie de Compiègne, 60205, Compiègne, France [A-S. B., D. M., C. B.]; Centre National de la Recherche Scientifique, UMR 1599, Institut Gustave Roussy, 94805 Villejuif, France [E. J., H. L. A. V., G. K.]; QLT PhotoTherapeutics, Inc., Vancouver, British Columbia, V5Z 4H5, Canada [D. J. G.]; and The Burnham Institute, La Jolla, California 92037 [Z. X., J. C. R.]

We report that the photosensitizer verteporfin kills lymphoma cells by an apoptotic process involving a dissipation of the mitochondrial inner transmembrane potential (m). Light-activated verteporfin-induced apoptosis was abolished by transfection with Bcl-2, a procedure reported to inhibit the mitochondrial permeability transition pore complex (PTPC). Verteporfin triggered the m loss in isolated mitochondria in vitro, and this effect was suppressed by bongrekic acid and cyclosporin A. Verteporfin plus light also permeabilized proteoliposomes containing the semipurified PTPC or the purified PTPC component adenine nucleotide translocator (ANT), yet had no effect on protein-free control liposomes. Verteporfin phototoxicity on ANT proteoliposomes was mediated by reactive oxygen species and was prevented by recombinant Bcl-2 or the adenine nucleotides ATP and ADP. In conclusion, verteporfin belongs to a class of clinically used chemotherapeutic agents acting on PTPC and ANT.

This article has been cited by other articles:

				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]

				K Petermeier, O Tatar, W Inhoffen, M Volker, B A Lafaut, S Henke-Fahle, F Gelisken, F Ziemssen, S Bopp, K U Bartz-Schmidt, et al. Verteporfin photodynamic therapy induced apoptosis in choroidal neovascular membranes Br. J. Ophthalmol., August 1, 2006; 90(8): 1034 - 1039. [Abstract] [Full Text] [PDF]

				M. S. Ricci and W.-X. Zong Chemotherapeutic approaches for targeting cell death pathways. Oncologist, April 1, 2006; 11(4): 342 - 357. [Abstract] [Full Text] [PDF]

				W.-X. Zong and C. B. Thompson Necrotic death as a cell fate. Genes & Dev., January 1, 2006; 20(1): 1 - 15. [Abstract] [Full Text] [PDF]

				I. E. Furre, S. Shahzidi, Z. Luksiene, M. T.N. Moller, E. Borgen, J. Morgan, K. Tkacz-Stachowska, J. M. Nesland, and Q. Peng Targeting PBR by Hexaminolevulinate-Mediated Photodynamic Therapy Induces Apoptosis through Translocation of Apoptosis-Inducing Factor in Human Leukemia Cells Cancer Res., December 1, 2005; 65(23): 11051 - 11060. [Abstract] [Full Text] [PDF]

				U. Fischer and K. Schulze-Osthoff New Approaches and Therapeutics Targeting Apoptosis in Disease Pharmacol. Rev., June 1, 2005; 57(2): 187 - 215. [Abstract] [Full Text] [PDF]

				F. VERRIER, B. MIGNOTTE, G. JAN, and C. BRENNER Study of PTPC Composition during Apoptosis for Identification of Viral Protein Target Ann. N.Y. Acad. Sci., December 1, 2003; 1010(1): 126 - 142. [Abstract] [Full Text] [PDF]

				M.-G. Lum and P. Nagley Two phases of signalling between mitochondria during apoptosis leading to early depolarisation and delayed cytochrome c release J. Cell Sci., April 15, 2003; 116(8): 1437 - 1447. [Abstract] [Full Text] [PDF]

				A.-S. Belzacq, H. L. A. Vieira, F. Verrier, G. Vandecasteele, I. Cohen, M.-C. Prevost, E. Larquet, F. Pariselli, P. X. Petit, A. Kahn, et al. Bcl-2 and Bax Modulate Adenine Nucleotide Translocase Activity Cancer Res., January 15, 2003; 63(2): 541 - 546. [Abstract] [Full Text] [PDF]

				K. Machida, Y. Hayashi, and H. Osada A Novel Adenine Nucleotide Translocase Inhibitor, MT-21, Induces Cytochrome c Release by a Mitochondrial Permeability Transition-independent Mechanism J. Biol. Chem., August 16, 2002; 277(34): 31243 - 31248. [Abstract] [Full Text] [PDF]

				D. J. Granville, B. A. Cassidy, D. O. Ruehlmann, J. C. Choy, C. Brenner, G. Kroemer, C. van Breemen, P. Margaron, D. W. Hunt, and B. M. McManus Mitochondrial Release of Apoptosis-Inducing Factor and Cytochrome c During Smooth Muscle Cell Apoptosis Am. J. Pathol., July 1, 2001; 159(1): 305 - 311. [Abstract] [Full Text] [PDF]