Synthetic uncouplers: Electron transport and phosphoryla- tion can also be uncoupled by compounds that increase the permeability of the inner mitochondrial membrane to protons. The classic example is 2,4-dinitrophenol, a lipophilic proton carrier that readily diffuses through the mitochondrial mem- brane. This uncoupler causes electron transport to proceed at a rapid rate without establishing a proton gradient, much as do the UCPs (see Figure 6.14). Again, energy is released as heat rather than being used to synthesize ATP. In high doses, aspirin and other salicylates uncouple oxidative phos - phorylation. This explains the fever that accompanies toxic overdoses of these drugs