Mitochondrial uncoupling proteins in the CNS: in support of function and survival.

Mitochondrial uncoupling mediated by uncoupling protein 1 (UCP1) is classically associated with non-shivering thermogenesis by brown fat. Recent evidence indicates that UCP family proteins are also present in selected neurons. Unlike UCP1, these proteins (UCP2, UCP4 and BMCP1/UCP5) are not constitutive uncouplers and are not crucial for non-shivering thermogenesis. However, they can be activated by free radicals and free fatty acids, and their activity has a profound influence on neuronal function. By regulating mitochondrial biogenesis, calcium flux, free radical production and local temperature, neuronal UCPs can directly influence neurotransmission, synaptic plasticity and neurodegenerative processes. Insights into the regulation and function of these proteins offer unsuspected avenues for a better understanding of synaptic transmission and neurodegeneration.