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].