Comparison of the effects on mitochondrial function of a series of 2-methyl substituted 1,4-naphthoquinones to their 6-methyl counterparts.

Seven derivatives of 2-methyl-1,4-naphthoquinone were compared to an equivalent series of 6-methyl-1,4-naphthoquinone derivatives for their abilities to interact with mitochondrial membranes and enzyme systems. The substituents on the methyl groups included various electron-withdrawing and -donating groups. The 6-methyl quinones were, in general, more potent inhibitors of NADH-oxidase and succinoxidase, depleted sulfhydryl groups more completely, produced greater rates of cyanide (CN-)-insensitive respiration (respiratory bursts), and induced more severe large-amplitude mitochondrial swelling than the analogous 2-methyl quinones. The NADH-oxidase system was more sensitive than succinoxidase to inhibition by both series, suggesting that Complex I is the primary site of inhibition by these quinones.