000095968 001__ 95968
000095968 005__ 20201027161503.0
000095968 0247_ $$2doi$$a10.1084/jem.187.8.1261
000095968 0248_ $$2sideral$$a116954
000095968 037__ $$aART-1998-116954
000095968 041__ $$aeng
000095968 100__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel
000095968 245__ $$aThe Permeability Transition Pore Complex: A Target for Apoptosis Regulation by Caspases and Bcl-2-related Proteins
000095968 260__ $$c1998
000095968 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095968 5203_ $$aEarly in programmed cell death (apoptosis), mitochondrial membrane permeability increases. This is at least in part due to opening of the permeability transition (PT) pore, a multiprotein complex built up at the contact site between the inner and the outer mitochondrial membranes. The PT pore has been previously implicated in clinically relevant massive cell death induced by toxins, anoxia, reactive oxygen species, and calcium overload. Here we show that PT pore complexes reconstituted in liposomes exhibit a functional behavior comparable with that of the natural PT pore present in intact mitochondria. The PT pore complex is regulated by thiol-reactive agents, calcium, cyclophilin D ligands (cyclosporin A and a nonimmunosuppressive cyclosporin A derivative), ligands of the adenine nucleotide translocator, apoptosis-related endoproteases (caspases), and Bcl-2-like proteins. Although calcium, prooxidants, and several recombinant caspases (caspases 1, 2, 3, 4, and 6) enhance the permeability of PT pore-containing liposomes, recombinant Bcl-2 or Bcl-XL augment the resistance of the reconstituted PT pore complex to pore opening. Mutated Bcl-2 proteins that have lost their cytoprotective potential also lose their PT modulatory capacity. In conclusion, the PT pore complex may constitute a crossroad of apoptosis regulation by caspases and members of the Bcl-2 family.
000095968 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-sa$$uhttp://creativecommons.org/licenses/by-nc-sa/3.0/es/
000095968 590__ $$a15.882$$b1998
000095968 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b2 / 72 = 0.028$$c1998$$dQ1$$eT1
000095968 591__ $$aIMMUNOLOGY$$b3 / 120 = 0.025$$c1998$$dQ1$$eT1
000095968 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095968 700__ $$aBrenner, Catherine
000095968 700__ $$aZamzami, Naoufal
000095968 700__ $$aSusin, Santos A.
000095968 700__ $$aBeutner, Gisela
000095968 700__ $$aBrdiczka, Dieter
000095968 700__ $$aRémy, René
000095968 700__ $$aXie, Zhi-Hua
000095968 700__ $$aReed, John C.
000095968 700__ $$aKroemer, Guido
000095968 773__ $$g187, 8 (1998), 1261-1271$$pJ. exp. med.$$tJOURNAL OF EXPERIMENTAL MEDICINE$$x0022-1007
000095968 8564_ $$s239206$$uhttps://zaguan.unizar.es/record/95968/files/texto_completo.pdf$$yVersión publicada
000095968 8564_ $$s602173$$uhttps://zaguan.unizar.es/record/95968/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095968 909CO $$ooai:zaguan.unizar.es:95968$$particulos$$pdriver
000095968 951__ $$a2020-10-27-15:04:01
000095968 980__ $$aARTICLE