Apoptosis induction by the photosensitizer verteporfin: Identification of mitochondrial adenine nucleotide translocator as a critical target

We report that the photosensitizer verteporfin kills lymphoma cells by an a poptotic process involving a dissipation of the mitochondrial inner transme mbrane potential (Delta Psim). Light-activated verteporfin-induced apoptosi s was abolished by transfection with Bcl-2, a procedure reported to inhibit the mitochondrial permeability transition pore complex (PTPC). Verteporfin triggered the Delta Psim 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 h ad no effect on protein-free control liposomes. Verteporfin phototoxicity o n ANT proteoliposomes was mediated by reactive oxygen species and mas preve nted by recombinant Bcl-2 or the adenine nucleotides ATP and ADP. In conclu sion, verteporfin belongs to a class of clinically used chemotherapeutic ag ents acting on PTPC and ANT.