Vacuolar H+-ATPases (V-ATPases) are large multisubunit proton pumps that are required for housekeeping acidification of\nmembrane-bound compartments in eukaryotic cells. Mammalian V-ATPases are composed of 13 different subunits. Their\nhousekeeping functions include acidifying endosomes, lysosomes, phagosomes, compartments for uncoupling receptors and\nligands, autophagosomes, and elements of the Golgi apparatus. Specialized cells, including osteoclasts, intercalated cells in the\nkidney and pancreatic beta cells, contain both the housekeeping V-ATPases and an additional subset of V-ATPases, which plays\na cell type specific role. The specialized V-ATPases are typically marked by the inclusion of cell type specific isoforms of one or\nmore of the subunits. Three human diseases caused by mutations of isoforms of subunits have been identified. Cancer cells utilize\nV-ATPases in unusual ways; characterization of V-ATPasesmay lead to new therapeutic modalities for the treatment of cancer. Two\naccessory proteins to the V-ATPase have been identified that regulate the proton pump. One is the (pro)renin receptor and data\nis emerging that indicates that V-ATPase may be intimately linked to renin/angiotensin signaling both systemically and locally. In\nsummary, V-ATPases play vital housekeeping roles in eukaryotic cells. Specialized versions of the pump are required by specific\norgan systems and are involved in diseases.
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