COMPARISON OF THE STRUCTURES OF THE QUINONE-BINDING SITES IN BEEF-HEART MITOCHONDRIA

The ubiquinone pool in mitochondrial membranes serves as an electron c arrier between both NADH-coenzyme Q oxidoreductase (Complex I) and suc cinate-coenzyme Q oxidoreductase (Complex II) and ubiquinol-cytochrome -c oxidoreductase (Complex III). It has been reported (Saitoh, I., Miy oshi, 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 mam malian mitochondria as well as in photosystem II. We have probed the s imilarities and differences in the reaction sites of exogenous Q in al l three segments of the respiratory chain using selected 2-alkyl-4,6-d initrophenols. The inhibition of Q analog reduction by the dinitrophen ol derivatives was competitive for Complex I and noncompetitive for Co mplex II. The inhibition of Complex III was competitive with the penty l analog, but was uncompetitive with the decyl analog, which may be du e to different interactions of the two quinol analogs with Complex III . The degree of inhibition by several of these compounds was comparabl e for Complexes I and III, but Complex II was inhibited to a much smal ler 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 ubiquino ne. Hydrophobic substituents increased the inhibition of Complex II. R eplacement of the phenolic OH group by a chlorine atom decreased the m aximum inhibition of Complex III, but increased that of Complex I. The se data suggest that the structures of the exogenous Q-binding sites i n Complexes I and Ill may be similar, but not identical, and that they are different from that in Complex II.