title: Mitochondria and nitric oxide: chemistry and pathophysiology.
abstract: Cell respiration is controlled by nitric oxide (NO) reacting with respiratory chain complexes, particularly with Complex I and IV. The functional implication of these reactions is different owing to involvement of different mechanisms. Inhibition of complex IV is rapid (milliseconds) and reversible, and occurs at nanomolar NO concentrations, whereas inhibition of complex I occurs after a prolonged exposure to higher NO concentrations. The inhibition of Complex I involves the reversible S-nitrosation of a key cysteine residue on the ND3 subunit. The reaction of NO with cytochrome c oxidase (CcOX) directly involves the active site of the enzyme: two mechanisms have been described leading to formation of either a relatively stable nitrosyl-derivative (CcOX-NO) or a more labile nitrite-derivative (CcOX-NO                   (2)                             (-)                 ). Both adducts are inhibited, though with different K(I); one mechanism prevails on the other depending on the turnover conditions and availability of substrates, cytochrome c and O(2). SH-SY5Y neuroblastoma cells or lymphoid cells, cultured under standard O(2) tension, proved to follow the mechanism leading to degradation of NO to nitrite. Formation of CcOX-NO occurred upon rising the electron flux level at this site, artificially or in the presence of higher amounts of endogenous reduced cytochrome c. Taken together, the observations suggest that the expression level of mitochondrial cytochrome c may be crucial to determine the respiratory chain NO inhibition pathway prevailing in vivo under nitrosative stress conditions. The putative patho-physiological relevance of the interaction between NO and the respiratory complexes is addressed.
authors.affiliation: Department of Biochemical Sciences, University of Rome, Rome, Italy. paolo.sarti@uniroma1.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Sarti
authors.forename: Marzia
authors.initials: M
authors.lastname: Arese
authors.forename: Elena
authors.initials: E
authors.lastname: Forte
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuffrè
authors.forename: Daniela
authors.initials: D
authors.lastname: Mastronicola
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*
chemical_list: D009569:Nitric Oxide