The flavonoid quercetin induces changes in mitochondrial permeability by inhibiting adenine nucleotide translocase.
This study shows the effects of the flavonoid quercetin on diverse mitochondrial functions, among them membrane permeability. Our findings indicate that the addition of 50 microM quercetin did not produce reactive oxygen derived species; however, it inhibited the oxidative stress induced after the addition of Fe(2)/H(2)O(2) by about 38%. At this concentration, quercetin also promoted a fast calcium release, inhibited oxidative phosphorylation, stimulated oxygen consumption, and decreased membrane potential. In addition 50 microM quercetin inhibited the adenine nucleotide translocase (ANT) by 46%. These effects induced the opening of the permeability transition pore and release of cytochrome c, by its interaction with a component of the non-specific pore complex, fixed to the carrier in the conformation c, as carboxyatractyloside does. Quercetin-induced permeability transition pore opening was inhibited by 0.5 microM cyclosporin A, but, interestingly, the release of cytochrome c was not inhibited by the immunosuppressor, as quercetin was found to disrupt the outer membrane.
Ortega
Rosalba
R
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1 Col. Sección XVI, Mexico, DF 14080, Mexico.
García
Noemí
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011794:Quercetin / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013696:Temperature; D017392:Thiobarbituric Acid Reactive Substances
D017392:Thiobarbituric Acid Reactive Substances; D000226:Mitochondrial ADP, ATP Translocases; D011794:Quercetin; D002118:Calcium