Nitrite reductase activity is a novel function of mammalian mitochondria

Abstract

Nitrite, which is the major stable degradation product of nitric oxide, exists in all tissues capable of nitric oxide synthesis from L-arginine. The present study provides experimental evidence that nitrite in contact with respiring mitochondria accepts reducing equivalents from the ubiquinone cycle of the respiratory chain. Univalent reduction of nitrite was totally inhibited by myxothiazol. We therefore conclude on the involvement of redox cycling that ubisemiquinone is associated with the bc 1 complex. Recycling of nitric oxide degradation products via these electron carriers may become a threat to energy-linked respiration since nitric oxide in direct contact with mitochondria was shown to slow the energy-linked respiration down and to trigger a mitochondrial source for superoxide radicals. Until now, the existence of nitrite reductase activity was only demonstrated in plants and bacteria. In addition, the present observation elucidates the existence of a nitric oxide synthaseindependent nitric oxide source.z 1999 Federation of European Biochemical Societies.

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

“…Nitrite reduction to nitric oxide is catalyzed by elements of the mitochondrial electron transport chain such as ubiquinol and cytochrome c oxidase (complex IV) under hypoxic conditions (151,152). The · NO produced has a high affinity for cytochrome c oxidase and may serve as a reversible inhibitor of mitochondrial respiration (vide supra) preventing ischemic reperfusion injury.…”

Mechanisms involved in the pro- and anti-apoptotic role of NO in human leukemia

“…Therefore, recycling of NO 2 via these electron carriers is a threat to energy-linked respiration since NO was shown to slow the energy-linked respiration down and to trigger a mitochondrial source for superoxide radicals. 46 …”

Bioanalytical profile of the l-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis

“…High-capacity NO production in eukaryotic systems has two dominant but not unique routes: 1) the primary production via enzymatic oxygenation of the guanidine group of L-arginine to form NO and L-citrulline by a specific enzyme, NO synthase (NOS) [17]; and 2) the secondary production by enzymatic reduction of nitrite [18,19] via nitrite reductase activity (NRA) of xanthine oxidase [20,21], mitochondrial cytochrome complexes [22,23], deoxyhemoglobin [24][25][26], and some NOS isozymes under anoxic conditions [27]. It is generally assumed that the primary NO synthesis from L-arginine oxidation by NOS and following retrograde diffusion of the gaseous messenger is responsible for focal "neurotransmitter-like" actions of NO [28], as well as for pathogen-induced escalation of cytotoxic defense [29].…”