Comparison of the structures of the quinone-binding sites in beef heart mitochondria.

The ubiquinone pool in mitochondrial membranes serves as an electron carrier between both NADH-coenzyme Q oxidoreductase (Complex I) and succinate-coenzyme Q oxidoreductase (Complex II) and ubiquinol-cytochrome-c oxidoreductase (Complex III). It has been reported (Saitoh, I., Miyoshi, H., Shimizu, R., and Iwamura, H. (1992) Eur. J. Biochem. 209, 73-79) that 2-alkyl-4,6-dinitrophenols compete with exogenous coenzyme Q (Q) to inhibit electron transport through cytochromes b and c1 in mammalian mitochondria as well as in photosystem II. We have probed the similarities and differences in the reaction sites of exogenous Q in all three segments of the respiratory chain using selected 2-alkyl-4,6-dinitrophenols. The inhibition of Q analog reduction by the dinitrophenol derivatives was competitive for Complex I and noncompetitive for Complex II. The inhibition of Complex III was competitive with the pentyl analog, but was uncompetitive with the decyl analog, which may be due to different interactions of the two quinol analogs with Complex III. The degree of inhibition by several of these compounds was comparable for Complexes I and III, but Complex II was inhibited to a much smaller extent. The inhibitory potency of these compounds for Complexes I and III was increased by branching and by lengthening the carbon chain at the 2-position equivalent to the isoprenoid side chain of ubiquinone. Hydrophobic substituents increased the inhibition of Complex II. Replacement of the phenolic OH group by a chlorine atom decreased the maximum inhibition of Complex III, but increased that of Complex I. These data suggest that the structures of the exogenous Q-binding sites in Complexes I and III may be similar, but not identical, and that they are different from that in Complex II.