Vacuolar-type ATPase (V-ATPase)

Vacuolar-type ATPase (V-ATPase) is a large, multi-subunit rotary enzyme complex responsible for ATP-dependent proton (H⁺) transport across the membranes of various intracellular organelles (including lysosomes, endosomes, and the Golgi apparatus) and in certain cell types at the plasma membrane. The enzyme is essential for acidification of organellar lumens, which is required for protein degradation, membrane trafficking, and signaling events. Structurally, it contains two main domains: the V₁ domain (ATP hydrolysis) and the V₀ domain (proton translocation). V-ATPase dysfunction is linked to numerous human diseases, including cancer, bone, and renal disorders. While some bacterial V-type ATPases (notably Enterococcus hirae) can directly pump sodium (Na⁺) instead of protons, this function is not found in human V-ATPases, and dedicated sodium pumps in humans use P-type ATPases (Na⁺/K⁺-ATPase). Therefore, “sodium-pumping V-type ATPase” refers specifically to certain prokaryotic enzymes and is not standard nomenclature for a therapeutic target in humans.

Other names

Vacuolar H⁺-ATPaseV-ATPaseV-type ATPaseV₁V₀-ATPase

Inhibitors block ATP-hydrolysis–driven proton translocation, preventing organelle acidification and associated cellular processes.