Vacuolar or V-type pumps are a type of ATP-driven pumps mainly present on the membranes of eukaryotic subcellular compartments like plant vacuoles, lysosomes, and endosomes.
V-type pumps are turbine-like structures with two domains— V1 and V0.
The transmembrane V0 domain comprises multiple subunits, including an a-subunit and a ring of membrane-spanning c-subunits.
The cytosolic V1 domain is also made up of numerous subunits, including a hexamer of alternating A and B subunits, a rotor, and peripheral stators.
Consider a V-type pump present on the lysosomal membrane of a eukaryotic cell.
As a molecule of ATP enters the hexameric subunit of the V1 domain, it gets hydrolyzed into ADP and inorganic phosphate.
The energy released from ATP hydrolysis rotates the central stalk and the c-ring subunits of the V0 domain.
A proton from the cytosol enters through a channel in the a-subunit and binds to a c-ring subunit.
Simultaneously, a lumen-facing channel of the a-subunit releases the proton into the lysosome making space for another proton to bind the c-subunit from the cytosol.
V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits helps transport protons. This proton translocation activity is vital for cellular processes such as pH homeostasis, endocytosis, protein trafficking, urine acidification, and neurotransmitter release.
While complete loss of the pump function can be lethal, mutations in the subunits are associated with renal tubular acidosis, osteoporosis, neurodegenerative disease, and others, making this pump a potential drug target.
Regulation of the pumps’ activity by different mechanisms ensures that the cell and its organelles maintain the proton gradient. The reversible dissociation of the V0 and V1 domains is due to several factors like nutrients and growth factors that can silence the activity of both subunits. For instance, the reversible disulfide bond formation at the cysteine residues of the A-subunit does not allow ATP hydrolysis to occur.
Modulation of the pump density is another control mechanism seen in epithelial cells. In renal epithelial cells, proton transport in alpha intercalated and epididymal clear cells is controlled by reversible fusion of intracellular vesicles containing a high density of V-type pumps with the apical membrane.
Leitura Sugerida
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Cipriano, Daniel J., Yanru Wang, Sarah Bond, Ayana Hinton, Kevin C. Jefferies, Jie Qi, and Michael Forgac. "Structure and regulation of the vacuolar ATPases." Biochimica et Biophysica Acta (BBA)-Bioenergetics 1777, no. 7-8 (2008): 599-604.
Grabe, Michael, Hongyun Wang, and George Oster. "The mechanochemistry of V-ATPase proton pumps." Biophysical Journal 78, no. 6 (2000): 2798-2813.