Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase.

By Guy C. Brown. Biochimica et Biophysica Acta, 2001

621 citations recorded by the source corpus.

Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by a variety of means. Nanomolar concentrations of NO immediately, specifically and reversibly inhibit cytochrome oxidase in competition with oxygen, in isolated cytochrome oxidase, mitochondria, nerve terminals, cultured cells and tissues. Higher concentrations of NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain, uncoupling, permeability transition, and/or cell death. Isolated mitochondria, cultured cells, isolated tissues and animals in vivo display respiratory inhibition by endogenously produced NO from constitutive isoforms of NO synthase (NOS), which may be largely mediated by NO inhibition of cytochrome oxidase. Cultured cells expressing the inducible isoform of NOS (iNOS) can acutely and reversibly inhibit their own cellular respiration and that of co-incubated cells due to NO inhibition of cytochrome oxidase, but after longer-term incubation result in irreversible inhibition of cellular respiration due to NO or its derivatives. Thus the NO inhibition of cytochrome oxidase may be involved in the physiological and/or pathological regulation of respiration rate, and its affinity for oxygen.

Subfields: Biochemistry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/cdf795ddaf4c293f5e6acb04c7aefdb4395504b3

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In Biochemistry

1. Guoyao Wu
2. Oliver Kann
3. R. Kovács
4. F. Aktan

In Molecular Biology

1. Michael R Hamblin
2. Guoyao Wu
3. Oliver Kann
4. R. Kovács
5. F. Aktan

In Physiology

1. Guoyao Wu
2. Oliver Kann
3. R. Kovács
4. S. Fried
5. Michael R Hamblin
6. F. Aktan

Citations in the corpus

• Inhibition of Respiration by Nitric Oxide Induces a Mycobacterium tuberculosis Dormancy Program (2003, background): “Comprehensive studies of human mitochondrial aa3-type cytochrome oxidase (7) (homologous to the aa3-type cytochrome oxidase from M.”
• Biphasic Dose Response in Low Level Light Therapy (2009, background): “Nitric oxide produced in the mitochondria can inhibit respiration by binding to Cox and competitively displacing oxygen, especially in stressed or hypoxic cells (Brown 2001).”
• Mitochondria and neuronal activity. (2007, background): “Nevertheless, this issue is very important because NO has been reported to block oxidative respiration, reversibly and irreversibly (25, 186).”
• iNOS-mediated nitric oxide production and its regulation. (2004, background): “Peroxynitrite can irreversibly inhibit mitochondrial respiration and damage a variety of mitochondrial components via oxidizing reactions (Brown, 2001).”
• Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. (2006, background): “Second, high levels of NO may directly modulate the activity of the mitochondrial electron transport system [74].”