IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Interaction of NO with mitochondrial Complex III: functional consequences and mechanism
Autor/es:
BOVERIS A; BOMBICINO SS; IGLESIAS DE; VALDEZ LB
Lugar:
Lisboa
Reunión:
Congreso; 19th Biennial Meeting for the Society for Free Radical Research International (SFRRI); 2018
Institución organizadora:
Society for Free Radical Research International (SFRRI)
Resumen:
Previous results from our laboratory showed that NO inhibits complex III producing antimycin-like effects regarding to the enhancements of [UQH●]ss, [cyt. b2+], and O2●- and H2O2 productions. In this work, the effects of NO solution (obtained by bubbling NO gas; 10% in N2), on complex III enriched fraction -isolated from bovine heart- were studied. Complex III activity was hyperbolic inhibited by NO (IC50=225 nM). The absorbance spectra of complex III exposed to NO showed the characteristic peak of cyt. bH2+ (562 nm). In coupled mitochondria, 1 M NO inhibited succinate-sustained state 3 O2 consumption (50%). Addition of HbO2 recovered O2 consumption by 90%; the remaining 10% was insensitive to NO scavenging, suggesting the blockage of complex III by NO. Moreover, mitochondria exposed to NO showed a less change in ΔΨ (30%) in the transition from state 4 to state 3 respiration, lowering ATP synthesis capacity. According to [UQH●]ss enhancement detected by EPR, H2O2 production rate was augmented (55%). Altogether, these results could be explained through a kinetic model which considers the interaction of NO with cyt. bH and, consequently, the inhibition of electron transfer between cytochromes b, the formation of UQH●, and the increase of O2●- and H2O2 production rates.