Directed proton transfer from Fo to F1 extends the multifaceted proton functions in ATP synthase

Cobra Venom Cytotoxins as a Tool for Probing Mechanisms of Mitochondrial Energetics and Understanding Mitochondrial Membrane Structure

“…Interestingly, one year after the same research group showed once again that the mitochondrial membrane acts as a conjugate base when it absorbs protons through its surface and as Brønsted acid when it releases protons as a substrate for ATP synthase [67]. In a recent review by Nesterov and Yaguzhinski [68], the role of protons in enabling conformational changes in the F1 subunit and in inducing the phosphorylation reaction (ADP → ATP) was emphasized. That comprehensive review postulated that protons passing through the Fo subunit do not leave to the bulk water but form a pH gradient between Fo and F1 that facilitates proton transfer to F1.…”

“…That comprehensive review postulated that protons passing through the Fo subunit do not leave to the bulk water but form a pH gradient between Fo and F1 that facilitates proton transfer to F1. Mechanistically, the protons passing through the Fo subunit bind to carboxyl groups of amino acid residues located within F1 to cancel electrostatic attraction between the charged amino acid residues of the rotor and stator, leading to conformational changes in the enzyme [68]. Protonation happens at the start of ATP synthesis and during phosphorylation, while deprotonation stops the rotation of Fo, which inhibits both ATP synthesis and hydrolysis.…”

“…Protonation happens at the start of ATP synthesis and during phosphorylation, while deprotonation stops the rotation of Fo, which inhibits both ATP synthesis and hydrolysis. Overall, the review listed the key roles of protons, including coupling in ATP synthase, transfer of charge and energy, facilitation of ATP rotation via conformational changes, and direct participation in the reaction of ATP synthesis [68].…”