ABSTRACT
The acidification of intracellular organelles is crucial for a wide
range of cellular processes including protein sorting in biosyn-
thetic and endocytic pathways; protein processing, activation and
degradation; membrane transport; and coupled transport of small
molecules [1-3]. Organelle acidification in all eukaryotic cells is
mediated by the vacuolar proton-translocating ATPase known as
V-ATPase. V-ATPases couple the energy released by hydrolysis of
cytoplasmic ATP to active transport of protons from the cytosol into
intracellular compartments. The proton gradient generated by the
V-ATPase is required to maintain the pH of intracellular organelles
and to regulate ion homeostasis [4]. V-ATPases have been shown
to play a significant role in cytoplasmic pH homeostasis as well
[5]. In addition to their role in intracellular pH regulation, some
cells express V-ATPases at the plasma membrane where they pump
protons from the cytosol out of the cell mediating cell-specific
functions, such as urine acidification, bone resorption, and sperm
maturation [2, 6, 7].