NITRIC-OXIDE AND PEROXYNITRITE EXERT DISTINCT EFFECTS ON MITOCHONDRIAL RESPIRATION WHICH ARE DIFFERENTIALLY BLOCKED BY GLUTATHIONE OR GLUCOSE

Nitric oxide (NO) and peroxynitrite both inhibit respiration by brain submitochondrial particles, the former reversibly at cytochrome c oxid ase, the latter irreversibly at complexes I-III. Both GSH (IC50 = 10 m u M) and glucose (IC50 = 8 mM) prevented inhibition of respiration by peroxynitrite (ONOO-), but neither glucose (100 mM) nor GSH (100 mu M) affected that by NO. Thus, unless ONOO- is formed within mitochondria it is unlikely to inhibit respiration in cells directly, because of r eactions with cellular thiols and carbohydrates. However, the reversib le inhibition of respiration at cytochrome c oxidase by NO is likely t o occur (e.g. in the brain during ischaemia) and could be responsible for cytotoxicity.