Table of Contents
New Journal of Science
Volume 2014, Article ID 675430, 21 pages
http://dx.doi.org/10.1155/2014/675430
Review Article

Vacuolar H+-ATPase: An Essential Multitasking Enzyme in Physiology and Pathophysiology

1Department of Orthodontics, University of Florida College of Dentistry, 1600 SW Archer Road Dental Tower D7-18, CB 100444, Gainesville, FL 32610, USA
2Department of Anatomy & Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA

Received 8 September 2013; Accepted 7 November 2013; Published 23 January 2014

Academic Editor: Dzung H. Dinh

Copyright © 2014 L. Shannon Holliday. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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