2.B.72.  The Usnic Acid Cation Exchanger (UACE) Family 

Usnic acid (UA) is a naturally occurring dibenzofuran derivative found in several lichin species with the formula C₁₈H₁₆O₇. It is a lichenic acid that accumulates in lichenized fungi.  It is a monobasic acid with dibenzofuran structure and antibiotic properties. It is a protonophoric uncoupler of oxidative phosphorylation, widely known as a weight-loss dietary supplement. In contrast to conventional proton-shuttling mitochondrial uncouplers, UA was found to carry protons across lipid membranes via the induction of an electrogenic proton exchange for calcium or magnesium cations, but various divalent metal cations can stimulate proton transport through both planar and vesicular bilayer lipid membranes. The transmembrane electrical current and fluorescence-detected pH gradient dissipation in pyranine-loaded liposomes were measured (Rokitskaya et al. 2022). The selectivity series of divalent cations was Zn²⁺ > Mn²⁺ > Mg²⁺ > Ca²⁺ >> Cu²⁺. Cu²⁺ appeared to suppress the UA-mediated proton transport in both lipid membrane systems. The data on the divalent metal cation/proton exchange were supported by circular dichroism spectroscopy of UA in the presence of the corresponding cations (Rokitskaya et al. 2022).