title: Copper induces permeability transition through its interaction with the adenine nucleotide translocase.
abstract: In this work we examined the effect of low concentrations of Cu(2+) on the opening of the mitochondrial non-specific pore. The purpose was addressed to further contribute to the knowledge of the mechanisms that regulate the open/closed cycles of the permeability transition pore. Membrane leakage was established by measuring matrix Ca(2+) efflux and mitochondrial swelling. The experimental results indicate that Cu(2+) at very low concentrations promoted the release of accumulated Ca(2+), as well as mitochondrial swelling, provided 1,10-phenanthroline has been added. Carboxyatractyloside and Cu(2+) exhibited additive effects on these parameters. After Cu(2+) titration of membrane thiols, it might be assumed that the blockage of 5.9nmol of SH/mg protein suffices to open the non-specific pore. Taking into account the reinforcing effect of carboxyatractyloside, the increasing ADP concentrations, and that N-ethylmaleimide inhibited the Cu(2+)-induced Ca(2+) efflux, it is proposed that the target site for Cu(2+) is located in the ADP/ATP carrier.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1, Tlalpam, DF 014080, México.
authors.forename: Noemí
authors.initials: N
authors.lastname: García
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Abundis
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavón
authors.forename: Francisco
authors.initials: F
authors.lastname: Correa
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D003300:Copper / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008634:Mersalyl / Q000494:pharmacology; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000302:isolation & purification; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017186:Titrimetry
chemical_list: D024101:Mitochondrial Proteins; D013438:Sulfhydryl Compounds; D001278:Atractyloside; D008634:Mersalyl; D000244:Adenosine Diphosphate; D003300:Copper; D000226:Mitochondrial ADP, ATP Translocases; D005978:Glutathione; D005033:Ethylmaleimide; C003853:carboxyatractyloside