Effect of long-chain fatty acids and acyl-CoA on mitochondrial permeability,transport, and energy-coupling processes

The following effects of fatty acids and acyl-CoA thioesters on energy metabolism of mitochondria can now be assumed: (1) Inhibition of adenine nucleotide translocation. This effect may increase the energy state of mitochondria respiring under state 3 conditions and decrease phosphorylation potential in the surrounding medium (the cytoplasm). (2) Increased permeability to monovalent cations. This may lead to a partial energy dissipation due to a futile recycling of K+ (or another cation), namely and energy-dependent uptake and a passive outflow. (3) True uncoupling due to increased permeability to protons. This effect probably occurs at high concentrations of fatty acids only. (4) Substrate effect. Fatty acids in the form of acyl-CoA are excellent respiratory substrates for mitochondria of most tissues. Their oxidation is coupled to the generation of high energy state of the mitochondrial membrane and, consequently, to ATP synthesis.     

Effect of monovalent cations on the inhibition by NAD+ of NADH oxidation in submitochondrial particles.

Oxidation of NADH in submitochondrial particles, with O₂ or ferricyanide as electron acceptor, was inhibited by micromolar concentrations of NAD⁺ when measured in 240 mM sucrose or, in a lesser extent, in 120 mM NaCl or LiCl. In 120 mM solutions of either KCl, RbCl, CsCl or NH₄Cl the inhibition by up to 100 μM concentrations of NAD⁺ did not occur. The inhibition observed in the sucrose medium disappeared after solubilization of the particles with detergents and re-appeared when the membranes were reconstituted. The inhibitory effect was potentiated by palmitoyl-CoA. The possibility is discussed that the inhibition of NADH oxidation by low concentrations of NAD⁺ and its release by K⁺, Rb⁺, Cs⁺ and NH₄⁺ depend on the interaction between NAD⁺ and the negatively charged mitochondrial membrane.