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An uncoupling protein (UCP) is a mitochondrial inner membrane protein that is a regulated proton channel or transporter. An uncoupling protein is thus capable of dissipating the proton gradient generated by NADH-powered pumping of protons from the mitochondrial matrix to the mitochondrial intermembrane space. The energy lost in dissipating the proton gradient via UCPs is not used to do biochemical work. Instead, heat is generated. This is what links UCP to thermogenesis. UCPs are positioned in the same membrane as the ATP synthase, which is also a proton channel. The two proteins thus work in parallel with one generating heat and the other generating ATP from ADP and inorganic phosphate, the last step in oxidative phosphorylation. Mitochondria respiration is coupled to ATP synthesis but is regulated by UCPs.

History

Scientists observed the thermogenic activity in brown adipose tissue, which eventually led to the discovery of the UCP. The brown tissue revealed elevated levels of mitochondria respiration and another respiration not coupled to ATP synthesis, which symbolized strong thermogenic activity. The UCP was the protein discovered responsible for activating a proton pathway that was not coupled to ADP phosphorylation.