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Aguirre 2010 Biochim Biophys Acta
Coupling states LEAK  + , ROUTINE  + , ET  +
Enzyme Complex IV;cytochrome c oxidase  +
Has abstract Nitric oxide (NO) inhibits mitochondrial r
Nitric oxide (NO) inhibits mitochondrial respiration by decreasing the apparent affinity of cytochrome c oxidase (CcO) for oxygen. Using iNOS-transfected HEK 293 cells to achieve regulated intracellular NO production, we determined NO and O<sub>2</sub> concentrations and mitochondrial O<sub>2</sub> consumption by high-resolution respirometry over a range of O<sub>2</sub> concentrations down to nanomolar. Inhibition of respiration by NO was reversible, and complete NO removal recovered cell respiration above its routine reference values. Respiration was observed even at high NO concentrations, and the dependence of IC<sub>50</sub> on [O<sub>2</sub>] exhibits a characteristic but puzzling parabolic shape; both these features imply that CcO is protected from complete inactivation by NO and are likely to be physiologically relevant. We present a kinetic model of CcO inhibition by NO that efficiently predicts experimentally determined respiration at physiological O<sub>2</sub> and NO concentrations and under hypoxia, and accurately predicts the respiratory responses under hyperoxia. The model invokes competitive and uncompetitive inhibition by binding of NO to the reduced and oxidized forms of CcO, respectively, and suggests that dissociation of NO from reduced CcO may involve its O<sub>2</sub> dependent oxidation. It also explains the non-linear dependence of IC<sub>50</sub> on O<sub>2</sub> concentration, and the hyperbolic increase of c<sub>50</sub> as a function of NO concentration.
sub> as a function of NO concentration.  +
Has info [ PMID: 20144583 Open Access]  +
Has publicationkeywords Nitric oxide  + , Mitochondrial respiration  + , Cytochrome c oxidase  + , Oxygen consumption  + , Mitochondria  + , Kinetic model  +
Has title Aguirre E, Rodríguez-Juárez F, Bellelli A, Gnaiger E, Cadenas S (2010) Kinetic model of the inhibition of respiration by endogenous nitric oxide in intact cells. Biochim Biophys Acta 1797:557-65.  +
Instrument and method Oxygraph-2k  + , NO  +
MiP area Respiration  + , Genetic knockout;overexpression  +
Pathways ROX  +
Preparation Intact cells  + , Enzyme  + , Oxidase;biochemical oxidation  +
Respiration and regulation Inhibitor  + , Oxygen kinetics  +
Stress Oxidative stress;RONS  +
Tissue and cell HEK  +
Was published by MiPNetLab ES Madrid Cadenas S + , AT Innsbruck Gnaiger E +
Was published in journal Biochim Biophys Acta +
Was published in year 2010  +
Was written by Aguirre E + , Rodriguez-Juarez F + , Bellelli A + , Gnaiger E + , Cadenas S +
Categories Publications
Modification date
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14:11:56, 27 March 2018  +
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