Physiological regulation of heart mitochondrial nitric oxide synthase

VALDEZ LB; ZAOBORNYJ T; BOMBICINO S; GONZALES GF; BOVERIS A

Free Radical Pathophysiology

Transworld Research Network

Lugar: Kerala, India; Año: 2008; p. 177 - 190

Heart submitochondrial membranes produce nitric oxide (NO) at a rate of 2.19 ± 0.10 nmol NO/min. mg protein. NO production has been observed not only in mitochondrial membranes, but also in coupled mitochondria, being the NO release 40 % lower in state 3 than in state 4. Heart mitochondrial NO production accounts for about 60 % of the total cellular NO generation, suggesting a central regulatory role of the mitochondrial NO in cardiomyocytes. Mitochondrial nitric oxide synthase (mtNOS) is a highly regulated enzyme which, in turn, plays a regulatory role through the establishment of mitochondrial NO steady state levels, that modulate O2 uptake and superoxide (O2•-) and hydrogen peroxide (H2O2) production rates. At 50-200 nM concentrations, NO exhibits two main effects on the mitochondrial respiratory chain: the competitive inhibition of cytochrome oxidase and the stimulation of O2•- production by the inhibition of the electron transfer at complex III. The ability of mtNOS to modulate mitochondrial O2 uptake and H2O2 production, by its product NO, is termed mtNOS functional activity, and is considered the main pathway by which NO exerts its role as an intracellular regulator in physiological, pathological and pharmacological conditions. Changes in mtNOS functional activity reflect variations in mitochondrial NO production and NO steady state concentrations. Hypoxia, ischemia-reperfusion, hypothyroidism, inflammation, apoptosis and aging, are biological situations in which the regulation of mitochondrial respiration by NO is considered important