Thermogenin (also known as uncoupling protein 1, or UCP1) is an uncoupling protein found in the mitochondria of brown adipose tissue (BAT). Thermogenin is found in brown adipose tissue (BAT) where it is used to generate heat by non-shivering thermogenesis. Non-shivering thermogenesis is the primary means of heat generation in hibernating mammals and in human infants.

Though some details remain controversial, the molecular mechanism of thermogenin mediated uncoupling is reasonably well understood; thermogenin provides an alternative pathway by which protons can reenter the mitochondrial matrix, allowing the energy stored by proton pumping to be dissipated in the form of heat. Like the ATP synthase, thermogenin is a proton channel in the mitochondrial inner membrane that permits the translocation of protons from the mitochondrial inter membrane space to the mitochondrial matrix. Unlike ATP synthase however, which ‘couples’ proton translocation to synthesis of ATP, thermogenin catalyzes a ‘wasteful’ proton leak across the mitochondrial inner membrane. It is termed an uncoupling protein because it ‘uncouples’ the mitochondrial proton gradient from the generation of ATP by ATP synthase.

Thermogenin was discovered in 1979and was first cloned in 1988^*. Uncoupling protein two (UCP2), a homolog of thermogenin, was identified in 1997. In the past decade three additional homologs of thermogenin have been identified, including UCP3, UCP4, and BMCP1 (also known as UCP5).

Termogenina