Fatty acid interaction with mitochondrial uncoupling proteins

The phenomena of fatty acid interaction with mitochondrial integral membran e proteins, namely uncoupling proteins (UCPs), are reviewed to emphasize th e fatty acid cycling mechanism that has been suggested to explain the UCP f unction. Fatty acid-induced uncoupling is suggested to serve in bioenergeti c systems, to set the optimum efficiency, and to tune the degree of couplin g of oxidative phosphorylation. Fatty acid interaction with the "classic" u ncoupling protein (UCP1) from mitochondria of thermogenic brown adipose tis sue (BAT) is well known. UCP1 is considered to mediate purine nucleotide-se nsitive uniport of monovalent unipolar anions, including anionic fatty acid s. The return of protonated fatty acid leads to H+ uniport and uncoupling. Experiments supporting this mechanism are also reviewed for plant uncouplin g mitochondrial protein (PUMP) and ADP/ATP carrier. The fatty acid cycling mechanism is predicted, as well for the recently discovered uncoupling prot eins, UCP2 and UCP3.