Ablation of Uncoupling Protein‐3 Does Not Inhibit Palmitate Export from Mouse Heart Mitochondria

Abstract

Uncoupling protein‐3 (UCP3) has been implicated in the export of long‐chain free fatty acid (FA) from mitochondria. However, there is no direct evidence of FA export from mitochondria. If UCP3 is involved in FA export from mitochondria then its ablation should inhibit the process. Employing a novel technique developed in our laboratory that directly measures FA export from isolated mitochondria, we sought to determine whether or not the rate of export of palmitate generated in the matrix from palmitoyl‐carnitine is inhibited in mitochondria isolated from UCP3 knockout (UCP3KO) mouse hearts. UCP3KO mouse heart mitochondria had no detectable UCP3 protein. However, the UCP2 level was similar to wild type mouse heart mitochondria. The mitochondrial thioesterase‐1 (MTE‐1) which generates FA in the matrix was increased by ~30% in UCP3 knockout compared to WT mice. The rate of generation of palmitate from palmitoyl‐carnitine in mitochondria was also increased by ~25%, but there was no inhibition in the rate of export of palmitate from mitochondria of UCP3KO mouse hearts. We conclude that UCP3 does not exclusively export FA from mitochondria.