Figure 1.

UCP1-mediated uncoupled respiration and its contribution to substrate oxidation. (A) In most mammalian cells, a proton motive force (PMF) created by the electron transfer chain (ETC) system is used by ATP synthase, resulting in ATP production (coupled respiration). To re-establish the electrochemical proton gradient across the inner mitochondrial membrane (IMM), the cells increase substrate oxidation, generating more NADH and FADH₂ needed by the ETC. However, for coupled respiration, the rate of substrate oxidation and electron flow through the ETC is highly dependent on ADP availability. (B) In brown adipocytes, the protons pass from the intermembrane space into the mitochondrial matrix through the membrane bound UCP1. The resulting proton leak causes a drop in the PMF, releasing heat but not ATP synthesis (uncoupled respiration). The futile cycle of ETC-mediated proton pumps and UCP1-mediated proton leak provides a marked capacity for brown adipocyte mitochondria to oxidize substrates independent of ADP availability. TCA, the tricarboxylic acid cycle; I, II, III, IV, ETC multi-subunit complexes I through IV; Q, coenzyme Q; Cyt c, cytochrome c; UCP1, uncoupled protein 1.