Figure 1.

Coupled and uncoupled respiration in thermogenic adipose tissues. Both coupled and uncoupled respiration occur in the mitochondria (inset). Following free fatty release and beta−oxidation, reducing equivalents nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH₂) are produced to be used in the electron transport chain. Electrons subsequently move through four enzymes (Complexes I–IV) and two mobile electron carriers (ubiquinone, Q, and cytochrome c) within the inner mitochondrial membrane, which results in protons moving to the intermembrane space. Movement of the aforementioned protons through Complex V back into the mitochondrial matrix is coupled to ATP production (a). During thermogenesis, uncoupling protein 1 (UCP1) is induced and promotes backflow of protons across the inner membrane. Protonic backpressure is reduced, leading to maximally accelerated NADH and FADH₂ formation, and oxidation is consequently uncoupled from phosphorylation, resulting in heat production instead of ATP generation (b). H⁺ = proton; e⁻ = electron; Q = ubiquinone; QH₂ = reduced ubiquinone, ubiquinol. Figure created with biorender.com.