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Nitric Oxide and Mitochondrial Complex IV
Author(s) -
Sarti Paolo,
Arese Marzia,
Bacchi Antonella,
Barone Maria Cecilia,
Forte Elena,
Mastronicola Daniela,
Brunori Maurizio,
Giuffrè Alessandro
Publication year - 2003
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540310001628726
Subject(s) - nitrite , cytochrome c oxidase , nitric oxide , adduct , chemistry , mitochondrion , enzyme , biochemistry , oxidase test , respiratory chain , oxidative phosphorylation , cytochrome , respiration , stereochemistry , nitrate , biology , organic chemistry , botany
Micromolar nitric oxide (NO) rapidly (ms) inhibits cytochrome c oxidase in turnover with physiological substrates. Two reaction mechanisms have been identified leading, respectively, to formation of a nitrosyl‐ [a32+‐NO] or a nitrite‐ [a33+‐NO2‐] derivative of the enzyme. In the presence of O2, the nitrosyl adduct recovers activity slowly, following NO displacement at k'≈0.01 s‐1 (37°C); the recovery of the nitrite adduct is much faster. Relevant to patho‐physiology, the enzyme does not degrade NO by following the first mechanism, whereas by following the second one it promotes NO oxidation and disposal as nitrite/nitrate. The reaction between NO and cytochrome c oxidase has been investigated at different integration levels of the enzyme, including the in situ state, such as in mouse liver mitochondria or cultured human SY5Y neuroblastoma cells. The respiratory chain is inhibited by NO, either supplied exogenously or produced endogenously via the NO synthase activation. Inhibition of respiration is reversible, although it remains to be clarified whether reversibility is always full and how it depends on concentration of and time of exposure to NO. Oxygraphic measurements show that cultured cells or isolated state 4 mitochondria exposed to micromolar (or less) NO recover from NO inhibition rapidly, as if the nitrite reaction was predominant. Mitochondria in state 3 display a slightly more persistent inhibition than in state 4, possibly due to a higher accumulation of the nitrosyl adduct. Among a number of parameters that appear to control the switch over between the two mechanisms, the concentration of reductants (reduced cytochrome c) at the cytochrome c oxidase site has been proved to be the most relevant one. IUBMB Life, 55: 605‐611, 2003