Nitric oxide as a competitive inhibitor of oxygen consumption in the mitochondrial respiratory chain

Abstract

Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by various means. The author and others have shown that low (nanomolar) concentrations of NO immediately, specifically and reversibly inhibit cytochrome oxidase in competition with oxygen, in isolated cytochrome oxidase, mitochondria, nerve terminals, cultured cells and tissues. Primary astrocytes and a macrophage cell line, activated by cytokines and endotoxin to express the inducible isoform of NO synthase, strongly and reversibly inhibited their own respiration and that of co-incubated cells by this means. Primary aortic endothelial cells transiently inhibited their own respiration when NO production was acutely stimulated with bradykinin or ATP, and basal NO release increased the apparent K_m for oxygen of respiration in these cells. Thus the NO inhibition of cytochrome oxidase may be involved in the physiological and/or pathological regulation of respiration rate and its affinity for oxygen.