VATPasepumpun

VATPasepumpun is a multi-subunit enzyme complex that uses energy from ATP hydrolysis to move protons across cellular membranes, thereby acidifying luminal compartments or the extracellular milieu. It belongs to the family of vacuolar-type H+-ATPases (V-ATPases), which drive proton translocation in many eukaryotic cells and some bacteria.

Structure and mechanism: The enzyme consists of two functional sectors: the peripheral V1 domain in the cytoplasm, which hydrolyzes ATP, and the membrane-embedded V0 domain, which translocates protons across the membrane. In mammals, the V1 sector contains subunits A–H and the V0 sector includes subunits a, c, c', c'', d, and e. ATP hydrolysis in V1 powers rotation that pumps protons through V0; the complex can reversibly disassemble into V1 and V0 to regulate activity in response to cellular conditions.

Distribution and function: V-ATPases are found in many eukaryotic cells. They acidify lysosomes, late endosomes, and the Golgi apparatus, enabling lysosomal proteolysis, receptor recycling, and cargo sorting. Some cell types, notably osteoclasts and certain renal tubule cells, place V-ATPases at the plasma membrane to acidify the extracellular space, which supports bone resorption and acid-base balance. In cancer, surface V-ATPases can contribute to tumor invasiveness by extracellular acidification.

Dysfunction and research: Defects in V-ATPase components cause lysosomal storage disorders and osteopetrosis, and abnormal activity is linked to neurodegenerative disease and cancer. Because V-ATPases are central to pH homeostasis, they are frequent targets in research; inhibitors such as bafilomycin A1 and concanamycin block activity and are used to study function, though systemic inhibition can be toxic.