0142200 - FGU-C 20010255 RIV US eng J - Článek v odborném periodiku
Jabůrek, M. - Vařecha, M. - Ježek, Petr - Garlid, K. D.
Alkylsulfonates as probes of uncoupling protein transport mechanism. Ion pair transport demonstrates that direct H(+) translocation by UCP1 is not necessary for uncoupling.
Journal of Biological Chemistry. Roč. 276, č. 34 (2001), s. 31897-31905. ISSN 0021-9258. E-ISSN 1083-351X
Grant CEP: GA AV ČR IAA5011106
Grant ostatní: NIH(US) DK56273
Výzkumný záměr: CEZ:AV0Z5011922
Klíčová slova: mitochondrial uncoupling proteins * alkylsulfonates * ion pair transport
Kód oboru RIV: CE - Biochemie
Impakt faktor: 7.258, rok: 2001

The mechanism of fatty acid-dependent uncoupling by mitochondrial uncoupling proteins (UCP) is still in debate. We have hypothesized that the anionic fatty acid head group is translocated by UCP, and the proton is transported electroneutrally in the bilayer by flip-flop of the protonated fatty acid. Alkylsulfonates are useful as probes of the UCP transport mechanism. They are analogues of fatty acids, and they are transported by UCP1, UCP2, and UCP3. We show that undecanesulfonate and laurate are mutually competitive inhibitors, supporting the hypothesis that fatty acid anion is transported by UCP1. Alkylsulfonates cannot be protonated because of their low pKa, consequently, they cannot catalyze electroneutral proton transport in the bilayer and cannot support uncoupling by UCP. We report for the first time that propranolol forms permeant ion pairs with the alkylsulfonates, thereby removing this restriction. Because a proton is transported with the neutral ion pair, the sulfonate is able to deliver protons across the bilayer, behaving as if it were a fatty acid. When ion pair transport is combined with UCP1, we now observe electrophoretic proton transport in UCP1 proteoliposomes and uncoupling of brown adipose tissue mitochondria. These experiments confirm that the proton transport of UCP-mediated uncoupling takes place in the lipid bilayer and not via UCP itself. Thus, UCP1, like other members of its gene family, translocates anions and does not translocate protons.
Trvalý link: http://hdl.handle.net/11104/0039907