Kidney Vacuolar H+-ATPase: Physiology and Regulation

The vacuolar H+-ATPase is a multisubunit protein consisting of a peripheral catalytic domain (V1) that binds and hydrolyzes adenosine triphosphate (ATP) and provides energy to pump H+ through the transmembrane domain (V0) against a large gradient. This proton-translocating vacuolar H+-ATPase is present in both intracellular compartments and the plasma membrane of eukaryotic cells. Mutations in genes encoding kidney intercalated cell–specific V0 a4 and V1 B1 subunits of the vacuolar H+-ATPase cause the syndrome of distal tubular renal acidosis. This review focuses on the function, regulation, and the role of vacuolar H+-ATPases in renal physiology. The localization of vacuolar H+-ATPases in the kidney, and their role in intracellular pH (pHi) regulation, transepithelial proton transport, and acid-base homeostasis are discussed.