FIGURE 14.

A tentative model of involvement of CoQ in UCP regulation. UCP-mediated uncoupling can be activated by free fatty acids (FFA), an effect that is sensitive to purine nucleotides (PNs). The CoQ redox state has no effect on basal and FFA-induced UCP-catalyzed H⁺ conductance in the absence of PNs, but it modulates the sensitivity of UCP to inhibition by PNs. At a given fatty acid concentration, increased CoQ reduction by the respiratory chain decreases the binding affinity of PN to UCP, possibly by directly interfering with PN binding to UCPs due to structural similarities, thereby promoting UCP activation. Conversely, at lower CoQH₂ levels, no negative regulation occurs and UCP activity is inhibited by PNs. Additionally, it has been proposed that altered levels of CoQ or its redox state potentially could affect ROS-mediated UCP activation through its antioxidant activity against lipid peroxidation. See glossary for other abbreviations.