vATPase

Vacuolar-type ATPase (V-ATPase) is a multisubunit enzyme complex that uses energy derived from ATP hydrolysis to pump protons (H+) across membranes. In most eukaryotic cells, V-ATPases acidify intracellular compartments such as endosomes, lysosomes, and the Golgi apparatus, where the low pH is required for enzyme activity, cargo processing, and protein sorting. Some cells also place V-ATPases on the plasma membrane, where they contribute to extracellular acidification and membrane potential regulation. V-ATPases are found in plants, animals, fungi, and many protists, and related A- and V-type ATPases occur in bacteria and archaea.

Structure and mechanism are organized around two functional domains. The cytosolic V1 domain hydrolyzes ATP and drives rotation of a central rotor, which in turn activates the membrane-embedded V0 domain to translocate protons across the membrane. The coupling between ATP hydrolysis and proton translocation creates an electrochemical gradient in the organelle lumen or at the cell surface. In principle, the proton motive force can drive ATP synthesis in reverse, but in living cells V-ATPases predominantly function as proton pumps.

Physiological roles are diverse. By acidifying organelles, V-ATPases regulate cargo sorting, receptor recycling, lysosomal enzyme activity, and autophagy. They also participate in processes such as protein processing in the Golgi and urine or bone resorption in specialized cells. Regulation occurs at the level of subunit assembly, reversible disassembly of V1 from V0 in some conditions, and tissue-specific expression.

Inhibitors such as bafilomycin A1 and concanamycin A are commonly used in research to study V-ATPase function. Abnormal V-ATPase activity has been linked to diseases including osteopetrosis, kidney disorders, and cancer, making them a target of therapeutic investigation.