Copper sensitizes the mitochondrial permeability transition to carboxytractyloside and oleate.
Addition of 5 microM copper to rat kidney mitochondria enhances the effect of carboxyatractyloside and oleate on pore opening, in a cyclosporin A-sensitive fashion. The effects of the pair copper-carboxyatractyloside were observed on matrix Ca2+ efflux, mitochondrial swelling and on the transmembrane electric gradient. The effect of Cu2+ emphasizes the importance of membrane thiol groups located, probably, in the ADP/ATP translocase (ANT), on permeability transition. It was also found that Cu2+ does not block the fluorescent label of ANT by eosin 5-maleimide, but abolishes the inhibition by CAT on the labeling. This suggests that the binding of Cu2+ to cysteine residues of ANT promotes a conformational change in the carrier, strengthening the effect of CAT and oleate on membrane leakage.
García
N
N
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, México, DF México.
Zazueta
C
C
Carrillo
R
R
Correa
F
F
Chávez
E
E
D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D010539:Permeability; D051381:Rats
D001278:Atractyloside; D019301:Oleic Acid; D003300:Copper; D000226:Mitochondrial ADP, ATP Translocases; C003853:carboxyatractyloside