Structure, function and regulation of the vacuolar (H+)-ATPases

FEBS Lett. 1998 Dec 4;440(3):258-63. doi: 10.1016/s0014-5793(98)01425-2.


The vacuolar (H+)-ATPases (or V-ATPases) function to acidify intracellular compartments in eukaryotic cells, playing an important role in such processes as receptor-mediated endocytosis, intracellular membrane traffic, protein degradation and coupled transport. V-ATPases in the plasma membrane of specialized cells also function in renal acidification, bone resorption and cytosolic pH maintenance. The V-ATPases are composed of two domains. The V1 domain is a 570-kDa peripheral complex composed of 8 subunits (subunits A-H) of molecular weight 70-13 kDa which is responsible for ATP hydrolysis. The V0 domain is a 260-kDa integral complex composed of 5 subunits (subunits a-d) which is responsible for proton translocation. The V-ATPases are structurally related to the F-ATPases which function in ATP synthesis. Biochemical and mutational studies have begun to reveal the function of individual subunits and residues in V-ATPase activity. A central question in this field is the mechanism of regulation of vacuolar acidification in vivo. Evidence has been obtained suggesting a number of possible mechanisms of regulating V-ATPase activity, including reversible dissociation of V1 and V0 domains, disulfide bond formation at the catalytic site and differential targeting of V-ATPases. Control of anion conductance may also function to regulate vacuolar pH. Because of the diversity of functions of V-ATPases, cells most likely employ multiple mechanisms for controlling their activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Endocytosis
  • Eukaryotic Cells
  • Ion Transport
  • Proton-Translocating ATPases / chemistry
  • Proton-Translocating ATPases / metabolism
  • Proton-Translocating ATPases / physiology*
  • Structure-Activity Relationship
  • Vacuolar Proton-Translocating ATPases*
  • Vacuoles / enzymology*
  • Vacuoles / physiology
  • Yeasts


  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases