scholarly journals Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose

1996 ◽  
Vol 314 (3) ◽  
pp. 877-880 ◽  
Author(s):  
Ignacio LIZASOAIN ◽  
Maria A. MORO ◽  
Richard G. KNOWLES ◽  
Victor DARLEY-USMAR ◽  
Salvador MONCADA
Keyword(s):  
Nitric Oxide ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiration ◽  
Submitochondrial Particles ◽  
Reversible Inhibition ◽  
The Brain ◽  
In Cells

Nitric oxide (NO) and peroxynitrite both inhibit respiration by brain submitochondrial particles, the former reversibly at cytochrome c oxidase, the latter irreversibly at complexes I–III. Both GSH (IC50 = 10 μM) and glucose (IC50 = 8 mM) prevented inhibition of respiration by peroxynitrite (ONOO-), but neither glucose (100 mM) nor GSH (100 μM) affected that by NO. Thus, unless ONOO- is formed within mitochondria it is unlikely to inhibit respiration in cells directly, because of reactions with cellular thiols and carbohydrates. However, the reversible inhibition of respiration at cytochrome c oxidase by NO is likely to occur (e.g. in the brain during ischaemia) and could be responsible for cytotoxicity.

scholarly journals Regulation of hypoxia-inducible factor-1α by nitric oxide through mitochondria-dependent and -independent pathways

2003 ◽  
Vol 376 (2) ◽  
pp. 537-544 ◽  
Author(s):  
Jesús MATEO ◽  
Marta GARCÍA-LECEA ◽  
Susana CADENAS ◽  
Carlos HERNÁNDEZ ◽  
Salvador MONCADA
Keyword(s):  
Nitric Oxide ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Mitochondrial Respiration ◽  
Hypoxia Inducible Factor ◽  
Human Cell Line ◽  
Α Subunit ◽  
High Concentrations ◽  
In Cells

Nitric oxide (NO) has been reported both to promote and to inhibit the activity of the transcription factor hypoxia-inducible factor-1 (HIF-1). In order to avoid the pitfalls associated with the use of NO donors, we have developed a human cell line (Tet-iNOS 293) that expresses the inducible NO synthase (iNOS) under the control of a tetracycline-inducible promoter. Using this system to generate finely controlled amounts of NO, we have demonstrated that the stability of the α-subunit of HIF-1 is regulated by NO through two separate mechanisms, only one of which is dependent on a functional respiratory chain. HIF-1α is unstable in cells maintained at 21% O2, but is progressively stabilized as the O2 concentration decreases, resulting in augmented HIF-1 DNA-binding activity. High concentrations of NO (>1 µM) stabilize HIF-1α at all O2 concentrations tested. This effect does not involve the respiratory chain, since it is preserved in cells lacking functional mitochondria (ρ0-cells) and is not reproduced by other inhibitors of the cytochrome c oxidase. By contrast, lower concentrations of NO (<400 nM) cause a rapid decrease in HIF-1α stabilized by exposure of the cells to 3% O2. This effect of NO is dependent on the inhibition of mitochondrial respiration, since it is mimicked by other inhibitors of mitochondrial respiration, including those not acting at cytochrome c oxidase. We suggest that, although stabilization of HIF-1α by high concentrations of NO might have implications in pathophysiological processes, the inhibitory effect of lower NO concentrations is likely to be of physiological relevance.

scholarly journals Cytochrome c oxidase maintains mitochondrial respiration during partial inhibition by nitric oxide

2006 ◽  
Vol 120 (1) ◽  
pp. 160-165 ◽  
Author(s):  
M. Palacios-Callender ◽  
V. Hollis ◽  
N. Frakich ◽  
J. Mateo ◽  
S. Moncada
Keyword(s):  
Nitric Oxide ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiration ◽  
Partial Inhibition

Sulphide as an inhibitor and electron donor for the cytochrome c oxidase system

1982 ◽  
Vol 60 (6) ◽  
pp. 613-623 ◽  
Author(s):  
P. Nicholls ◽  
J.-K. Kim
Keyword(s):  
Cytochrome C ◽  
Oxygen Uptake ◽  
Cytochrome C Oxidase ◽  
Submitochondrial Particles ◽  
Inhibitory Interaction ◽  
Cytochromes C ◽  
Subsequent Step ◽  
Oxidase Enzyme ◽  
Rapid Reaction ◽  
The One

Anomalies both kinetic and equilibrium in nature are described for the inhibition of cytochrome c oxidase activity by sulphide in the isolated enzyme and in submitochondrial particles. These anomalies are related to the involvement of more than 1 mol of sulphide in the blockage of one cytochrome aa3 centre. Sulphide reduces resting cytochrome a3, a reaction that results in oxygen uptake and the loss of a sulphide molecule. Sulphide can also reduce cytochromes c and a; in the former case, a part of the one-equivalent oxidation product, presumed to be the SH∙ radical, reacts with oxygen. Such oxygen uptake is also seen under aerobic conditions when ferricyanide reacts with sulphide. Three phases are identified in the inhibitory interaction of sulphide with the cytochrome c oxidase enzyme itself: an initial rapid reaction involving sulphide oxidation, oxygen uptake, and conversion of cytochrome aa3 into the low-spin "oxyferri" form; a subsequent step in which sulphide reduces cytochrome a; and the final inhibitory step in which a third molecule of sulphide binds the a3 iron centre in the cytochrome [Formula: see text] (oxy) species to give cytochrome [Formula: see text]. The initial events parallel some of the events in the interaction of the cytochrome c – cytochrome aa3 system with monothiols; the final inhibitory event resembles that with cyanide.

Reversible dimerization of cytochrome c oxidase regulates mitochondrial respiration

Mitochondrion ◽  
2019 ◽  
Vol 49 ◽  
pp. 149-155 ◽  
Author(s):  
Rabia Ramzan ◽  
Annika Rhiel ◽  
Petra Weber ◽  
Bernhard Kadenbach ◽  
Sebastian Vogt
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiration ◽  
Reversible Dimerization
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