Nitric oxide interacts with complex III producing antimycin-like effects

IGLESIAS DE; BOMBICINO SS; BOVERIS A; VALDEZ LB

Dresden

Congreso; 10th European Biophysics Congress - EBSA 2015; 2015

European Biophysical Societies´Association (EBSA)

The interaction of NO with mitochondrial complex III was studied using submitochondrial particles (SMP) from bovine heart and GSNO and SPER-NO as NO sources. Complex II-III activity (222±4 nmol/min.mg protein) was inhibited by 50% in the presence of 500 μM GSNO or 30 μM SPERNO, in both cases 1.25 μM NO. This effect was not due to the inhibition of complex II activity. Complex II-III activity was also decreased (36%) by endogenously produced NO.GSNO (500 μM) reduced cytochrome b562 by 71%, in an [O2] independent manner, and produced a hyperbolic increase in O2- (up to 1.3±0.1 nmol/min.mg protein) and H2O2 (up to 0.64±0.05 nmol/min.mg protein) productions. Succinate energized SMP showed an EPR signal (g=1.99) compatible with a stable semiquinone, which was increased by GSNO and SPER-NO. These signals were not modified under N2 atmosphere, discarding the effect of NOx species. The absence of an EPR signal compatible with a mono nitrosyl iron complex (MNIC) allows excluding the disruption of the Fe2S2 cluster by a MNIC formation. These results show that NO interacts with ubiquinone-cytochrome b area independently on [O2] producing antimycin-like effects, i.e. inhibition of electron transfer with an [UQH.]ss enhancement which sustains an increase in O2- and H2O2 production rates.