Mitochondria and Nitric Oxide: Chemistry and Pathophysiology

摘要: Cell respiration is controlled by nitric oxide (NO) reacting with respiratory chain complexes, particularly Complex I and IV. The functional implication of these reactions different owing to involvement mechanisms. Inhibition complex IV rapid (milliseconds) reversible, occurs at nanomolar NO concentrations, whereas inhibition after a prolonged exposure higher concentrations. involves the reversible S-nitrosation key cysteine residue on ND3 subunit. reaction cytochrome c oxidase (CcOX) directly active site enzyme: two mechanisms have been described leading formation either relatively stable nitrosyl-derivative (CcOX-NO) or more labile nitrite-derivative (CcOX-NO 2 − ). Both adducts are inhibited, though KI; one mechanism prevails other depending turnover conditions availability substrates, O2. SH-SY5Y neuroblastoma cells lymphoid cells, cultured under standard O2 tension, proved follow degradation nitrite. Formation CcOX-NO occurred upon rising electron flux level this site, artificially in presence amounts endogenous reduced c. Taken together, observations suggest that expression mitochondrial may be crucial determine pathway prevailing vivo nitrosative stress conditions. putative patho-physiological relevance interaction between complexes addressed.