Vacuolar proton-translocating ATPase (V-ATPase)

Vacuolar proton-translocating ATPase (Vacuolar-type H+-ATPase, V‑ATPase) is a highly conserved multisubunit enzyme complex found in all eukaryotic cells. It functions as a rotary proton pump that uses the energy from ATP hydrolysis to transport protons across intracellular membranes—acidifying compartments such as endosomes, lysosomes, and the Golgi apparatus—and sometimes across the plasma membrane. This acidification is crucial for numerous cellular processes including receptor-mediated endocytosis, protein degradation/maturation, vesicular trafficking, autophagy regulation, and maintenance of cytosolic pH homeostasis. The enzyme consists primarily of two domains: a peripheral catalytic domain (V₁) responsible for ATP hydrolysis and an integral membrane domain (V₀) responsible for translocating protons.\n\nIn disease contexts—especially cancer—upregulation or dysregulation of V‑ATPases contributes to tumor cell survival by supporting altered metabolism (e.g., glycolysis), promoting drug resistance through extracellular drug extrusion via acidified vesicles/extracellular space, and enabling invasive behavior. Pharmacological inhibitors like bafilomycin A1 block its activity but are limited by toxicity due to disruption of essential physiological functions in normal tissues. Overexpression or specific subunit alterations may serve as biomarkers for certain cancers such as glioblastoma.[1][3][4][6][7]

Other names

Vacuolar-type H+-ATPaseVacuolar-type ATPaseV-type ATPaseProton-translocating vacuolar ATPase

Inhibition of proton pumping by blocking the rotary catalytic mechanism or binding to specific subunits, leading to loss of organelle acidification and disruption of cellular processes dependent on acidic pH