Synergetic inhibition of the brain mitochondrial NADH: Ubiquinone oxidoreductase (Complex I) by fatty acids and Ca2+

The NADH:ubiquinone oxidoreductase (respiratory complex I) activity of inside-out pig brain submitochondrial particles is inhibited by endogenous or externally added free fatty acids in time-dependent fashion. The rate and degree of the inhibition is dramatically increased by Ca2+. The Ca2+-promoted, fatty acid-induced inhibition is pH dependent, this being particularly evident at pH > 8.0. The inhibition is completely reversed by either EGTA or by bovine serum albumin (BSA). BSA prevents previously described (Kotlyar, A. B., Sled, V. D., and Vinogradov, A. D. (1992) Biochim. Biophys. Acta, 1098, 144–150) inhibitory effect of Ca2+ and alkaline pH on the de-active-to-active form transition of complex I. A possible mechanism of synergetic inhibition on complex I by Ca2+ and fatty acids is discussed.