Fig. 1

Schematic depiction of cAMP- and Zn²⁺-mediated lysosomal acidification. Increases in cAMP levels through activation of adenylyl cyclase and/or inhibition of PDEs activate PKA. PKA activation leads to increases in lysosomal free Zn²⁺ levels by an as yet unidentified mechanism. Increases in lysosomal Zn²⁺ levels restore lysosomal acidity through an unknown mechanism, even in the presence of BA, a potent and selective inhibitor of the main proton pump, V-ATPase