Aguirre 2010 Biochim Biophys Acta
| Aguirre E, Rodriguez-Juarez 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: 557-565. |
» [[Has info::PMID: 20144583]]
Aguirre E, Rodriguez-Juarez F, Bellelli A, Gnaiger E, Cadenas S (2010) Biochim. Biophys. Acta
Abstract: [[has abstract::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 O2 concentrations and mitochondrial O2 consumption by high-resolution respirometry over a range of O2 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 IC50 on [O2] 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 O2 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 O2 - dependent oxidation. It also explains the non-linear dependence of IC50 on O2 concentration, and the hyperbolic increase of c50 as a function of NO concentration.]] • Keywords: Nitric oxide; Mitochondrial respiration; Cytochrome c oxidase; Oxygen consumption; Mitochondria; Kinetic model
• O2k-Network Lab: AT_Innsbruck_GnaigerE
Labels:
Stress:Hypoxia, RONS; Oxidative Stress, Genetic Defect; Knockdown; Overexpression Organism: Human Tissue;cell: Kidney Preparation: Intact Cell; Cultured; Primary, Oxidase; Biochemical Oxidation, Enzyme
Regulation: Respiration; OXPHOS; ETS Capacity, Coupling; Membrane Potential
HRR: Oxygraph-2k, MultiSensor pH; TPP; NO, Chemicals; Media, Theory
