Figure 1.

Mitochondrial respiration and uncoupling. During cellular respiration, the oxidation of substrates such as glucose and fatty acids [1] yields electrons (e⁻) in the form of reduced hydrogen carriers, NADH and FADH₂, which are donated to a series of enzyme complexes embedded in the inner mitochondrial membrane (IMM), ultimately reducing oxygen to water [2]. As electrons are transferred along the electron transport chain (ETC), a fixed number of protons (H⁺) are pumped across the IMM, generating a membrane potential (Δψm) and proton motive force that is subsequently used to drive the synthesis of ATP from ADP and inorganic phosphate [3]. Proton leak induced by chemical uncouplers [4] or uncoupling proteins (UCPs) [5] competes for the same proton gradient, resulting in lower Δψm and diminished production of ATP, accelerating mitochondrial respiration to maintain energy homeostasis. This figure was adapted from “Electron Transport Chain” by BioRender.com (2020). Retrieved from https://app.biorender.com/biorender-templates.