Analysis of the pathways of nitric oxide utilization in mitochondria |
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Authors: | Enrique Cadenas Juan José Poderoso Fernando Antunes Alberto Boveris |
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Institution: | 1. Department of Molecular Pharmacology &2. Toxicology, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089-9121, USA;3. Laboratory of Oxygen Metabolism, University Hospital, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina;4. Laboratory of Free Radical Biology, School of Pharmacy &5. Biochemistry, University of Buenos Aires, Buenos Aires, Argentina |
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Abstract: | The regulatory role that mitochondria play in cell dysfunction and cell-death pathways involves the concept of a complex and multisite regulation of cellular respiration and energy production signaled by cellular and intercellular messengers. Hence, the role of nitric oxide, as a physiological regulator acting directly on the mitochondrial respiratory chain acquires further relevance. This article provides a survey of the major regulatory roles of nitric oxide on mitochondrial functions as an expression of two major metabolic pathways for nitric oxide consumption: a reductive pathway, involving mitochondrial ubiquinol and yielding nitroxyl anion and an oxidative pathway involving superoxide anion and yielding peroxynitrite. The modulation of the decay pathways for nitrogen-and oxygen-centered radicals is further analyzed as a function of the redox transitions of mitochondrial ubiquinol. The interplay among these redox processes and its implications for mitochondrial function is discussed in terms of the mitochondrial steady-state levels (and gradients) of nitric oxide and superoxide anion. |
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Keywords: | mitochondria nitric oxide peroxynitrite cytochrome oxidase oxygen radicals nitrogen radicals peroxynitrite |
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