95968 20201027161503.0 doi 10.1084/jem.187.8.1261 sideral 116954 ART-1998-116954 eng (orcid)0000-0002-2315-9079 Marzo, Isabel The Permeability Transition Pore Complex: A Target for Apoptosis Regulation by Caspases and Bcl-2-related Proteins 1998 Access copy available to the general public Unrestricted Early in programmed cell death (apoptosis), mitochondrial membrane permeability increases. This is at least in part due to opening of the permeability transition (PT) pore, a multiprotein complex built up at the contact site between the inner and the outer mitochondrial membranes. The PT pore has been previously implicated in clinically relevant massive cell death induced by toxins, anoxia, reactive oxygen species, and calcium overload. Here we show that PT pore complexes reconstituted in liposomes exhibit a functional behavior comparable with that of the natural PT pore present in intact mitochondria. The PT pore complex is regulated by thiol-reactive agents, calcium, cyclophilin D ligands (cyclosporin A and a nonimmunosuppressive cyclosporin A derivative), ligands of the adenine nucleotide translocator, apoptosis-related endoproteases (caspases), and Bcl-2-like proteins. Although calcium, prooxidants, and several recombinant caspases (caspases 1, 2, 3, 4, and 6) enhance the permeability of PT pore-containing liposomes, recombinant Bcl-2 or Bcl-XL augment the resistance of the reconstituted PT pore complex to pore opening. Mutated Bcl-2 proteins that have lost their cytoprotective potential also lose their PT modulatory capacity. In conclusion, the PT pore complex may constitute a crossroad of apoptosis regulation by caspases and members of the Bcl-2 family. info:eu-repo/semantics/openAccess by-nc-sa http://creativecommons.org/licenses/by-nc-sa/3.0/es/ 15.882 1998 MEDICINE, RESEARCH & EXPERIMENTAL 2 / 72 = 0.028 1998 Q1 T1 IMMUNOLOGY 3 / 120 = 0.025 1998 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Brenner, Catherine Zamzami, Naoufal Susin, Santos A. Beutner, Gisela Brdiczka, Dieter Rémy, René Xie, Zhi-Hua Reed, John C. Kroemer, Guido 187, 8 (1998), 1261-1271 J. exp. med. JOURNAL OF EXPERIMENTAL MEDICINE 0022-1007 239206 http://zaguan.unizar.es/record/95968/files/texto_completo.pdf Versión publicada 602173 http://zaguan.unizar.es/record/95968/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:95968 articulos driver 2020-10-27-15:04:01 ARTICLE