Biochemistry and physiology of heart mitochondrial nitric oxide synthase

Abstract

Heart mitochondria are the major source of reactive oxygen and nitrogen species and play a central role in cell energy provision and signaling. The NO produced by cardiac mtNOS is allowed to interact restrictedly with the co-localized effectors. NO exerts a high affinity, reversible and physiological inhibition of cytochrome c oxidase activity. A second effect of NO on the respiratory chain is accomplished through its interaction with ubiquinol-cytochrome c oxidoreductase. The ability of mtNOS to regulate mitochondrial O2 uptake and O2 − and H2O2 productions is named mtNOS functional activity. Several situations, including chronic hypoxia and ischemia-reperfusion, modify heart mtNOS activity or expression. The regulation of heart mtNOS by distinctive mitochondrial environments includes the effects of Ca2+, O2, L-arginine, NADPH, mitochondrial membrane potential (Δψ) and the metabolic states. Together, this enzyme seems to be critical during the adaptation of heart mitochondria to changes in cellular bioenergetics.