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.

Keywords: renal vacuolar H⁺-ATPase, ATP6V1B1 subunit, ATP6V0A4 subunit, distal tubular renal acidosis (dRTA)