Effects of the mitochondrial uncoupling protein 3 on fuel substrate oxidation and reactive oxygen species formation in rat L6 muscle cells

Uncoupling protein 3 (UCP3) is an integral mitochondrial membrane protein thought to disassociate fuel substrate oxidation by allowing proton re-entry into the mitochondrial matrix. Expression of UCP3 has been correlated with fatty acid and glucose metabolism, and reactive oxygen species (ROS) formation. To improve our understanding of the potential involvement of UCP3 in such pathways we investigated the effects of a UCP3 overexpression (2.2-2.5 fold) in the L6 muscle cell line. These findings were compared to those of UCP2 overexpression and DNP exposure. Palmitate oxidation was significantly increased by overexpressing UCP3 but unaffected by the other treatment conditions. Both glucose oxidation and oxygen consumption were unaffected by UCP2 and UCP3 overexpression but were significantly increased by DNP treatment. ROS production was decreased by UCP2, UCP3 and DNP treatment. These findings suggest a role for UCP3 in the regulation of fatty acid oxidation and ROS formation but not in glucose oxidation