Mitochondrial Nitric‐oxide Synthase: Role in Pathophysiology

Abstract

SummaryThe biochemistry of the mitochondrial production of nitric oxide is reviewed to gain insight into the basic role of this radical in mitochondrial and cellular oxidative metabolism. The mitochondrial production of nitric oxide is catalyzed by a nitric-oxide synthase (mtNOS). This enzyme has the same cofactor and substrate requirements as other constitutive nitric-oxide synthases. Its occurrence was demonstrated in various mitochondrial preparations from different organs and species using diverse approaches (oxidation of oxymyoglobin, electron paramagnetic resonance in conjunction with spin trap, radiolabeled L-arginine, immunohistochemistry, nitric-oxide electrode). MtNOS has been identified as the alpha isoform of nNOS, acylated at a Thr or Ser residue, and phosphorylated at the C-terminal end. Endogenous nitric oxide reversibly inhibits oxygen consumption and ATP synthesis by competitive inhibition of cytochrome oxidase. Nitric oxide is the first molecule that fulfills the requirement for a cytochrome oxidase activity modulator: it is a competitive inhibitor, produced endogenously at a fair rate near the target site, at concentrations high enough to exhibit an inhibitory effect on cytochrome oxidase. The role of the mitochondrial nitric oxide production is discussed in terms of the physiological (modulating oxygen gradients into tissues) and pathological (abrogation of oxygen gradient modification, apoptosis, protein nitrative/oxidative stress) implications. IUBMB Life, 55: 599-603, 2003

Nitric oxide regulation of myocardial O2consumption and HEP metabolism

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The role of signalling molecules on actin glutathionylation and protein carbonylation induced by cadmium in haemocytes of musselMytilus galloprovincialis(Lmk)

“…There is evidence that the signalling molecules PKC and PI 3-kinase are involved in the regulation of phagocytosis, possibly through activation of NADPH oxidase and NO synthase (Baggiolini et al, 1986;Klebanoff, 1988;Torreilles et al, 1996;Thomas et al, 2002;Garcia-Garcia and Rosales, 2002;Garcia-Garcia, 2005;Haynes et al, 2003). The involvement of PKA in NO synthesis has been also suggested (Novas et al, 2004).…”

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