Why is inorganic phosphate necessary for uncoupling of oxidative phosphorylation by Cd2+ in rat liver mitochondria?
The phosphate (Pi)-dependent uncoupling action of Cd2+ in oxidative phosphorylation in rat liver mitochondria was studied mainly in terms of Pi transport. Cd2+ at 2 microM caused full uncoupling in the presence of 10 mM Pi, but no uncoupling in the absence of Pi. Cd2+ released state 4 respiration after a certain lag-time, and then the respiration increased progressively with time. After its addition, Cd2+ was taken up by mitochondria in a similar period to the lag time before respiratory release. KIH-201, a potent and specific inhibitor of Pi transport via the Pi/H+ symporter, abolished the uncoupling completely. Cd2+ caused dissipation of the electric transmembrane potential (delta psi) and swelling of mitochondria in a Pi-dependent manner. Uncoupling by Cd2+ was found to take place in parallel with the uptake of Pi into mitochondria via the Pi/H+ symporter, suggesting that the uncoupling was due to acceleration of H+ influx through the Pi/H+ symporter activated by Cd2+.
Koike
H
H
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Shinohara
Y
Y
Terada
H
H
D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red / Q000494:pharmacology
D010710:Phosphates; D002104:Cadmium; D012430:Ruthenium Red