Nitric oxide exerts an antimycin-like effect on rat heart mitochondria and submitochondrial particles.

PODEROSO JJ; CARRERAS MC; PERALTA JG; LISDERO C; SCHÖPFER F; RIOBÓ N; BOVERIS A

Pasadena, EEUU

Congreso; Annual Meeting of the Oxygen Society. Oxygen 1995; 1995

Exogenous nitric oxide (NO) and peroxynitrite have inhibitory effects on mitochondrial function and enzyme activities like aconitase and cytochrome c oxidase. As mitochondria can produce superoxide anion (O2-) and release hydrogen peroxide (H2O2) the main purpose of this study was to measure these compounds when heart mitochondria or submitochondrial particles were exposed to NO released by the S-nitrogluthatione donor (GSNO). Incubation of mitochondria with 25-150 µM GSNO (effective [NO] between 0.3 and 1.8 µM) induced a progressive increase in H2O2 release with 8 mM succinate alone which increased further with 2 µM antimycin (AA). The same effect was observed respect to both O2- and H2O2 in the isolated submitochondrial particles. The spectral analysis of cytochromes in the 500-650 nm range showed changes consistent with partial reduction of cyt b, similar to those induced by antimycin; simultaneous differential spectra showed that addition of succinate reduced cyt a-a3 but cyt b remained partially oxidized. Inhibition of region II-III of electron transfer chain by NO reached 80% with 1.2 µM [NO] and was partially reversible either by washing particles or by MbO2. The control organelles and particles showed no detectable H2O2 release with succinate but a similar response to AA. The results suggest that NO exerts an antimycin-like effect and increases O2 free radicals release by mitochondrial membranes.