Mechanism of uncoupling protein action.
Garlid, K.D., Jaburek, M. and Jezek, P. (2001) Mechanism of uncoupling
protein action, Biochem Soc Trans 29, 803-6.
Abstract:
Two competing models of uncoupling protein (UCP) transport mechanism agree
that fatty acids (FAs) are obligatory for uncoupling, but they disagree about
which ion is transported. In Klingenberg's model, UCPs conduct protons. In
Garlid's model, UCPs conduct anions, like all members of this gene family.
In the latter model, UCP transports the anionic FA head group from one side
of the membrane to the other, and the cycle is completed by rapid flip-flop
of protonated FAs across the bilayer. The head groups of the FA analogues,
long-chain alkylsulphonates, are translocated by UCP, but they cannot induce
uncoupling, because these strong acids cannot be protonated for the flip-flop
part of the cycle. We have overcome this limitation by ion-pair transport
of undecanesulphonate with propranolol, which causes the sulphonate to deliver
protons across the membrane as if it were an FA. Full GDP-sensitive uncoupling
is seen in the presence of propranolol and undecanesulphonate. This result
confirms that the mechanism of UCP uncoupling requires transport of the anionic
FA head group by UCP and that the proton transport occurs via the bilayer
and not via UCP.