UCP1: A transporter for H+ and fatty acid anions

Recently, the patch-clamp technique was successfully applied to the inner mitochondrial membrane of brown fat to directly characterize the H+ currents carried by UCP1. Based on the patch-clamp data, a new model of UCP1 operation was proposed. In brief, FA anions are transport substrates of UCP1, and UCP1 operates as an unusual FA anion/H+ symporter. Interestingly, in contrast to short-chain FA anions, long-chain FA anions cannot easily dissociate from UCP1 due to strong hydrophobic interactions established by their carbon tails, and a single long-chain FA participates in many H+ transport cycles. Therefore, in the presence of long-chain FA, endogenous activators of brown fat thermogenesis, UCP1 effectively operates as an H+ uniport. In addition to their transport function, long-chain FA competitively remove tonic inhibition of UCP1 by cytosolic purine nucleotides, thus enabling activation of the thermogenic H+ leak through UCP1 under physiological conditions.