Derivatives of the cationic plant alkaloids berberine and palmatine amplify protonophorous activity of fatty acids in model membranes and mitochondria

Previously it has been shown by our group that berberine and palmatine, penetrating cations of plant origin, when conjugated with plastoquinone (SkQBerb and SkQPalm), can accumulate in isolated mitochondria or in mitochondria of living cells and effectively protect them from oxidative damage. In the present work, we demonstrate that SkQBerb, SkQPalm, and their analogs lacking the plastoquinone moiety (C10Berb and C10Palm) operate as mitochondria-targeted compounds facilitating protonophorous effect of free fatty acids. These compounds induce proton transport mediated by small concentrations of added fatty acids both in planar and liposomal model lipid membranes. In mitochondria, such an effect can be carried out by endogenous fatty acids and the adenine nucleotide translocase.

► Сonjugates of berberine or palmatine (SkQBerb and SkQPalm) accumulate mitochondria.
► SkQBerb, SkQPalm and analogs lacking plastoquinone moiety operate as uncouplers.
► These compounds induce proton transport mediated by fatty acids.
► Their protonophorous action can be mediated by adenine nucleotide translocase.