Vacuolar Proton Pump (V-ATPase)

The vacuolar proton pump, also known as vacuolar-type H⁺-ATPase (V-ATPase), operates in the membranes of various organelles within eukaryotic cells, such as vacuoles, lysosomes, endosomes, the Golgi apparatus, and some vesicles. It also functions in the plasma membrane of certain specialized cells.

Function

The V-ATPase pumps protons (H⁺ ions) into intracellular compartments or out of the cell:

• Acidification: V-ATPase acidifies organelles like vacuoles and lysosomes, creating an acidic environment necessary for enzyme activity and various cellular processes.
• Ion Transport and Homeostasis: It maintains ion gradients across membranes, crucial for functions including nutrient storage, protein degradation, and receptor-mediated endocytosis.
• Vesicular Trafficking: The proton gradients established by V-ATPase are essential for vesicular trafficking and fusion.
• Bone Resorption: In osteoclasts, V-ATPase acidifies the resorption lacuna, which dissolves bone mineral.

Structure

The V-ATPase is a large, multi-subunit complex composed of two main domains:

• V₁ Domain: The peripheral catalytic sector hydrolyzes ATP and converts energy from ATP into mechanical work.
• V₀ Domain: The integral membrane sector contains the proton channel and translocates H⁺ ions across the membrane.

Regulation

Various factors regulate the activity and assembly of V-ATPase:

• Reversible Dissociation: The V₁ and V₀ domains can dissociate reversibly, regulating enzyme activity.
• Subunit Isoforms: Different cells express distinct isoforms of V-ATPase subunits, affecting the enzyme’s activity and localization.
• Post-Translational Modifications: Phosphorylation and other post-translational modifications influence V-ATPase activity.

Clinical Significance

Malfunction or dysregulation of V-ATPase associates with various diseases:

• Renal Tubular Acidosis: Defective V-ATPase in kidney cells impairs acid secretion and leads to metabolic acidosis.
• Osteopetrosis: Mutations affecting V-ATPase function in osteoclasts impair bone resorption and result in excessive bone density.
• Neurodegenerative Diseases: Abnormalities in lysosomal V-ATPase activity implicate disorders like Parkinson’s disease and Alzheimer’s disease.

Source | Glossary of Most Commonly Used Biomedical Terms and Concepts | Lithuanian University of Health Sciences | Academician Professor Antanas Praškevičius, Professor Laima Ivanovienė