The Rockefeller University Press

Vesicular H+-ATPases (V-ATPases) function as ATP-driven pro-ton pumps in intracellular compartments, such as endosomes, Golgi-derived vesicles, secretory vesicles, synaptic vesicles, lysosomes, and vacuoles (Forgac, 2007). Acidification is impor-tant for a plethora of cell biological processes ranging from endosomal ligand–receptor dissociation to lysosomal degrada-tion (Yan et al., 2009; Williamson et al., 2010; Zoncu et al., 2011). Consequently, interfering with V-ATPase function leads to direct and indirect defects that are difficult to tease apart. In addition, acidification-independent roles of the V-ATPase in secretion and membrane fusion have been proposed (Israël et al.