Regulation and function of V-ATPases in physiology and disease

Biochim Biophys Acta Biomembr. 2020 Dec 1;1862(12):183341. doi: 10.1016/j.bbamem.2020.183341. Epub 2020 May 16.


The vacuolar H+-ATPases (V-ATPases) are essential, ATP-dependent proton pumps present in a variety of eukaryotic cellular membranes. Intracellularly, V-ATPase-dependent acidification functions in such processes as membrane traffic, protein degradation, autophagy and the coupled transport of small molecules. V-ATPases at the plasma membrane of certain specialized cells function in such processes as bone resorption, sperm maturation and urinary acidification. V-ATPases also function in disease processes such as pathogen entry and cancer cell invasiveness, while defects in V-ATPase genes are associated with disorders such as osteopetrosis, renal tubular acidosis and neurodegenerative diseases. This review highlights recent advances in our understanding of V-ATPase structure, mechanism, function and regulation, with an emphasis on the signaling pathways controlling V-ATPase assembly in mammalian cells. The role of V-ATPases in cancer and other human pathologies, and the prospects for therapeutic intervention, are also discussed.

Keywords: Acidification; Cancer metastasis; Nutrient sensing; Proton transport; Regulated assembly; Vacuolar ATPase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Cell Membrane / metabolism
  • Humans
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Osteopetrosis / metabolism
  • Osteopetrosis / pathology*
  • Signal Transduction
  • Vacuolar Proton-Translocating ATPases / chemistry
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism*


  • Vacuolar Proton-Translocating ATPases