Proton leak through the UCPs and ANT carriers and beyond: A breath for the electron transport chain

Mitochondria produce heat as a result of an ineffective H⁺ cycling of mitochondria respiration across the inner mitochondrial membrane (IMM). This event present in all mitochondria, known as proton leak, can decrease protonmotive force (Δp) and restore mitochondrial respiration by partially uncoupling the substrate oxidation from the ADP phosphorylation. During impaired conditions of ATP generation with F₁F_O-ATPase, the Δp increases and IMM is hyperpolarized. In this bioenergetic state, the respiratory complexes support H⁺ transport until the membrane potential stops the H⁺ pump activity. Consequently, the electron transfer is stalled and the reduced form of electron carriers of the respiratory chain can generate O₂∙¯ triggering the cascade of ROS formation and oxidative stress. The physiological function to attenuate the production of O₂∙¯ by Δp dissipation can be attributed to the proton leak supported by the translocases of IMM.