FIG. 1.

General organization of mitochondrial electron transfer chain and the formation of O₂ species are modulated by NO. Electrons from reduced metabolites from the intermediary metabolism and tricarboxylic cycle enter the respiratory chain as NADH (to NADH dehydrogenase at complex I) or from succinate (to succinate dehydrogenase at complex II) and lead to a two-step reduction of reduced ubiquinol (to semiubiquinone, and ubiquinone). This sequential pathway finally reduces O₂ to water and, depending on electron entrance, extrudes two or three protons that creates an inner membrane potential and re-enter by ATP synthase with dissipation of energy and formation of ATP. From a low to high concentration, NO progressively inhibits cytochrome oxidase, complex II-III, and complex I. Myx, myxothiazole; AA, antimycin A; FeS, Fe sulfur complex; Cyt, cytochrome; SUCC, succinate; FUM, fumarate.