Figure 1.

Mitochondrial uncouplers increase mitochondrial respiration. Mitochondrial uncouplers mediate proton (H⁺) transport into the mitochondrial matrix via a pathway independent of ATP synthase [9,10]. Uncouplers bind to protons in the intermembrane space proceeding to cross the inner mitochondrial membrane (IMM). Mitochondrial protonophore uncouplers are typically lipophilic weak acids that can penetrate membranes [18]. Once an uncoupler has crossed the IMM, it is deprotonated and cycles out of the mitochondrial matrix, where it becomes protonated again to continue the uncoupling cycle. This figure was created with BioRender.com and adapted from Demine et al. [17].