Physiological role of UCP3 may be export of fatty acids from mitochondria when fatty acid oxidation predominates: An hypothesis

This hypothesis proposes a physiological role for uncoupling protein-3 (UCP 3) in the export of fatty acid anions from muscle and brown adipose tissue (BAT) mitochondria when fatty acids are the predominant substrate being use d. It proposes that excess acyl CoA within the mitochondria is hydrolyzed b y a mitochondrial acyl CoA thioesterase, yielding fatty acid anion and CoAS H. The fatty acid anion is exported to the cytosol by being carried across the inner mitochondrial membrane by UCP3. The CoASH is conserved within the mitochondrion to participate in other reactions for which it is needed dur ing fatty acid oxidation in the p-oxidation cycle and in the tricarboxylic acid cycle. The export of the fatty acid anion thus permits continued rapid fatty acid oxidation in the face of an oversupply. The hypothesis provides a logical explanation for the observed up-regulation of gene expression fo r UCP3 in muscle when there is a switch to fatty acid oxidation, as during fasting, and in BAT when fatty acid oxidation is stimulated, as during expo sure to cold. It provides a plausible physiological role for UCP3 as a tran sporter protein, not as an uncoupling protein.