Fig. 5.

Brain UCP2 in axons predicts increased mitochondrial proton leak and heat production. Light (A, B) and electron (C) micrographs demonstrate the abundant expression of UCP2 in presynaptic axon terminals. Arrows on the light micrographs ofA and B point to UCP2-containing presynaptic terminals in the central amygdaloid nucleus that establish symmetrical synapses (C, arrowheads) on the postsynaptic target. D, The measurement of mitochondrial respiration in brain regions (left panel) where UCP2 is present (hypothalamus) and where no UCP2 was detected (thalamus/striatum) showed a lower mitochondrial phosphorylation level (lower RCR) in the hypothalamus that was caused exclusively by an increased proton leak of mitochondria in UCP2-containing regions.E, In agreement with this increased mitochondrial uncoupling activity, brain temperature in the UCP2-expressing hypothalamus was significantly higher than that of the thalamus (right panel) and the core body temperature.F, The presence of UCP2 in axon terminals together with the significant, positive correlation between UCP2 and mitochondrial uncoupling and local brain temperature suggests that heat produced presynaptically by UCP2 may have a direct influence on axonal temperature leading to the modulation of presynaptic and postsynaptic events.