Figure 8. Hypothetical model showing potential role of UCP4-mediated proton leak in facilitating Complex II-mediated oxidative phosphorylation and ATP synthesis.

UCP4 may span in close proximity to Complex II on the mitochondrial inner membrane to increase regional proton concentration in the matrix, and facilitate subsequent reduction of ubiquinone (UQ) via heme-group to increase Complex II activity. Proton leak via UCP4 may increase regional proton supply near Complex II, which boosts proton transport in the downstream respiratory Complex III and IV. Net effect is a facilitation of high-energy electron flow along the respiratory chain to increase ATP synthesis.