Vacuolar H+-ATPases (V-ATPases) are a class of rotary ATPase that utilize the energy from ATP hydrolysis to pump protons against a membrane potential. This process serves to acidify intracellular compartments and generate transmembrane electrochemical potential gradients in eukaryotic cells [1]. V-ATPases are composed of two rotary motors: a soluble V1 that hydrolyses ATP and a transmembrane Vo that pumps protons (Fig. 1). These motors are coupled together by a central rotor and three peripheral stalks. This arrangement facilitates the transfer of torque from the V1 to the Vo motor [1 ]. The activity of the complex must be regulated to prevent ATP hydrolysis when cellular ATP concentrations are low or when acidification is not needed. Regulation is achieved by a reversible dissociation process, in which the V1 motor decouples from the Vo motor (Fig. 1). Subsequently, both motors are halted, silencing ATPase activity and proton flow [2].
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