Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology

  title={Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology},
  author={Michael Forgac},
  journal={Nature Reviews Molecular Cell Biology},
  • M. Forgac
  • Published 1 November 2007
  • Biology
  • Nature Reviews Molecular Cell Biology
The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation. At the heart of regulating acidity are the vacuolar (V-)ATPases — large, multisubunit complexes that function as ATP-driven proton pumps. Their activity is controlled by regulating the assembly of the V-ATPase complex or by the dynamic regulation of V-ATPase expression on membrane surfaces… 
Regulation and isoform function of the V-ATPases.
A number of mechanisms are employed to regulate V-ATPase activity in vivo, including reversible dissociation of the V(1) and V(0) domains, control of the tightness of coupling of proton transport and ATP hydrolysis, and selective targeting of V- ATPases to distinct cellular membranes.
Function, structure and regulation of the vacuolar (H+)-ATPases.
Regulation and function of V-ATPases in physiology and disease.
Recent Insights into the Structure, Regulation, and Function of the V-ATPases.
Vacuolar-type ATPases in animal and plant cells
Protons (H) play vital roles in bioenergetics and ion homeostasis, as evidenced by the presence of unique acidic compartments both inside and outside of cells. The acidification of compartments
The vacuolar (H+)-ATPase: subunit arrangement and in vivo regulation
Cysteine-mediated cross-linking has been used to localize subunit isoforms within the V-ATPase complex and to investigate the helical interactions between subunits within the integral V0 domain.
Structure and regulation of the vacuolar ATPases.
The curious case of vacuolar ATPase: regulation of signaling pathways
The direct role of V-ATPase in acidification and indirect regulation of signaling pathways, particularly Notch Signaling is discussed.
The Function of V-ATPases in Cancer.
Of greatest excitement is evidence that at least some tumors express isoforms of V-ATPase subunits whose disruption is not lethal, leading to the possibility of developing anti-cancer therapeutics that selectively target V- ATPases that function in cancer cells.


The vacuolar (H+)-ATPases — nature's most versatile proton pumps
The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including intracellular membrane transport, prohormone processing
The Where, When, and How of Organelle Acidification by the Yeast Vacuolar H+-ATPase
  • P. Kane
  • Biology
    Microbiology and Molecular Biology Reviews
  • 2006
Current knowledge of the structure, function, and regulation of the V- ATPase in S. cerevisiae is discussed and the relationship between biosynthesis and transport of V-ATPase and compartment-specific regulation of acidification is examined.
Subunit Rotation of Vacuolar-type Proton Pumping ATPase
This study genetically introduced a His tag and a biotin tag onto the c and G subunits, respectively, of Saccharomyces cerevisiae V-ATPase, and observed directly the continuous counter-clockwise rotation of an actin filament attached to the G subunit.
Three-dimensional Structure of the Vacuolar ATPase Proton Channel by Electron Microscopy*
The three-dimensional structure of the proton channel domain of the vacuolar ATPase from bovine brain clathrin-coated vesicles is determined by electron microscopy at 21 Å resolution.
Physical Interaction between Aldolase and Vacuolar H+-ATPase Is Essential for the Assembly and Activity of the Proton Pump*
Functional analysis of the aldolase mutants shows that disruption of binding between a Aldolase and the B subunit of V-ATPase results in disassembly and malfunction of V -ATPasing, which strongly suggest an important role for physical association between aldlase and V- ATPase in the regulation of the proton pump.
The V-type H+ ATPase: molecular structure and function, physiological roles and regulation
The V-type H+ ATPase is an ATP-driven enzyme that transforms the energy of ATP hydrolysis to electrochemical potential differences of protons across diverse biological membranes via the primary active transport of H+.
A Journey from Mammals to Yeast with Vacuolar H+-ATPase (V-ATPase)
  • N. Nelson
  • Biology
    Journal of bioenergetics and biomembranes
  • 2003
It was the survival of the yeast mutant without the active enzyme and yeast genetics that allowed the identification of genuine subunits of the V-ATPase, and revealed special properties of individual subunits, factors that are involved in the enzyme's biogenesis and assembly, as well as the involvement of V- ATPase in the secretory pathway, endocytosis, and respiration.
Vacuolar H+-ATPase d2 subunit: molecular characterization, developmental regulation, and localization to specialized proton pumps in kidney and bone.
In mouse, as in human, kidney and bone are two of the main sites of d2 mRNA expression, and a different subunit association in different tissues emphasizes the possibility of the H+-ATPase as a future therapeutic target.
Renal vacuolar H+-ATPase.
The importance in final urinary acidification along the collecting system is highlighted by monogenic defects in two subunits (ATP6V0A4, ATP6V1B1) of the vacuolar H(+)-ATPase in patients with distal renal tubular acidosis.