Ricardo Lagoa - Complex I and cytochrome c are molecular targets of flavonoids that inhibit hydrogen peroxide production by mitochondria

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      Publication Details (including relevant citation   information):

      Biochimica et Biophysica   Acta - Bioenergetics, 1807 (12), 1562-1572,   2011

      R. Lagoa, I. Graziani, C. Lopez-Sanchez, V. Garcia-Martinez   and C. Gutierrez-Merino


      Flavonoids can   protect cells from different insults that lead to   mitochondria-mediated cell death, and epidemiological data show   that some of these compounds attenuate the progression of   diseases associated with oxidative stress and mitochondrial   dysfunction. In this work, a screening of 5 flavonoids   representing major subclasses showed that they display different   effects on H2O2 production by mitochondria isolated from rat   brain and heart. Quercetin, kaempferol and epicatechin are potent   inhibitors of H2O2 production by mitochondria from both tissues   (IC50 approximately 1-2 μM), even when H2O2 production rate was   stimulated by the mitochondrial inhibitors rotenone and antimycin   A. Although the rate of oxygen consumption was unaffected by   concentrations up to 10 μM of these flavonoids, quercetin,   kaempferol and apigenin inhibited complex I activity, while up to   100 μM epicatechin produced less than 20% inhibition. The extent   of this inhibition was found to be dependent on the concentration   of coenzyme Q in the medium, suggesting competition between the   flavonoids and ubiquinone for close binding sites in the complex.   In contrast, these flavonoids did not significantly inhibit the   activity of complexes II and III, and did not affect the redox   state of complex IV. However, we have found that epicatechin,   quercetin and kaempferol are able to stoichiometrically reduce   purified cytochrome c. Our results reveal that mitochondria are a   plausible main target of flavonoids mediating, at least in part,   their reported preventive actions against oxidative stress and   mitochondrial dysfunction-associated pathologies.

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