Hypothesis on energy storage by membrane proton buffers: Connections to sleep and memory

Extramitochondrial ATP synthesis appears widespread thanks to the formation of mitochondrial-derived vesicles (MDVs) that export the mitochondrial molecular machinery of oxidative phosphorylation (OXPHOS) to cellular and extracellular membrane systems, where OXPHOS can occur in two phases: first, protons are charged into membrane proton buffers, and then, "discharge" occurs with the coupled synthesis of ATP. The capacitance of membrane proton buffers increases in the presence of abundant basic proteins (such as the myelin sheath, which contains nearly 30% myelin basic protein) allowing the first phase of OXPHOS to optimally charge the proton buffer, which then allows for an efficient discharge phase with the synthesis of large amounts of ATP. This provides an energy storage function that was not predicted by the chemiosmotic theory. Since memory depends on the accumulation and expenditure of brain energy, possible connections between energy buffers and memory are being considered. This study reevaluates the experiments of Russian scientists who, half a century ago, achieved a biphasic oxidative phosphorylation with intermediate proton accumulation by an artificial hydrophobic proton buffer embedded in the lipid phase.