Uncoupling of oxidative phosphorylation by divalent cationic cyanine dye. Participation of phosphate transporter.

The trinuclear cationic cyanine dye tri-S-C4(5) was found to be an uncoupler of oxidative phosphorylation. Its uncoupling required inorganic phosphate (Pi) or arsenate, which is transported into mitochondria via the Pi transport system, and was abolished by the Pi-transport inhibitor N-ethylmaleimide or mersalyl. The dye stimulated Pi uptake into mitochondria, and its uncoupling action was accompanied by swelling of the mitochondria. The adenine nucleotides ADP and ATP protected mitochondria from uncoupling by the dye. The dye taken up by mitochondria was released into the incubation medium on induction of uncoupling. In the absence of Pi, the dye did not cause uncoupling, but its uptake was much greater than in the presence of Pi. The cyanine dye is suggested to induce uncoupling by acting on the membrane, rather than after its electrophoretic transfer into the mitochondria.