New insights into the regulation of V-ATPase-dependent proton secretion.

The vacuolar H(+)-ATPase (V-ATPase) is a key player in several aspects of cellular function, including acidification of intracellular organelles and regulation of extracellular pH. In specialized cells of the kidney, male reproductive tract and osteoclasts, proton secretion via the V-ATPase represents a major process for the regulation of systemic acid/base status, sperm maturation and bone resorption, respectively. These processes are regulated via modulation of the plasma membrane expression and activity of the V-ATPase. The present review describes selected aspects of V-ATPase regulation, including recycling of V-ATPase-containing vesicles to and from the plasma membrane, assembly/disassembly of the two domains (V(0) and V(1)) of the holoenzyme, and the coupling ratio between ATP hydrolysis and proton pumping. Modulation of the V-ATPase-rich cell phenotype and the pathophysiology of the V-ATPase in humans and experimental animals are also discussed.