Channel character of uncoupling protein-mediated transport

Abstract 

Mitochondrial uncoupling proteins (UCPs) are pure anion uniporters, which mediate fatty acid (FA) uniport leading to FA cycling. Protonated FAs then flip-flop back across the lipid bilayer. An existence of pure proton channel in UCPs is excluded by the equivalent flux-voltage dependencies for uniport of FAs and halide anions, which are best described by the Eyring barrier variant with a single energy well in the middle of two peaks. Experiments with FAs unable to flip and alkylsulfonates also support this view. Phylogenetically, UCPs took advantage of the common FA-uncoupling function of SLC25 family carriers and dropped their solute transport function.

Abbreviations: ANT, adenine nucleotide transporter, i.e. ADP/ATP carrier, BLM, bilayer (black) lipid membrane, FA(s), fatty acid(s), FAOOH or FAOOH–COOH, fatty acid hydroperoxides, PUFAs, polyunsaturated fatty acids, PUMPn, plant uncoupling mitochondrial protein, isoform n, ROS, reactive oxygen species, SPQ, 6-methoxy-N-(3-sulfopropyl)-quinolinium, TEA, tetraethyl ammonium, TES, N-tris(hydroxymethyl)-methylamino-ethanesulfonic acid, UCP, UCPn, any uncoupling protein, isoform n

Keywords: Mitochondrial uncoupling protein, Fatty acid anion uniport, Anion uniport, Proton conductance, Eyring barrier model for transport