V-type proton ATPase subunit c (ATP6V0C)

V-type proton ATPase subunit c, encoded by the ATP6V0C gene, is a highly conserved 16 kDa proteolipid that forms the essential c-ring of the V0 rotary sector in the vacuolar-type H+-ATPase (V-ATPase) complex. This enzyme complex utilizes the energy from ATP hydrolysis to pump protons across biological membranes, a process vital for acidifying intracellular compartments such as lysosomes, endosomes, and secretory vesicles (UniProt P27449). Proper acidification is necessary for diverse cellular processes, including receptor-mediated endocytosis, protein sorting, and the activation of lysosomal hydrolases. In pathological contexts, ATP6V0C is often upregulated in various cancers, where it facilitates an acidic tumor microenvironment that promotes protease activation, extracellular matrix degradation, and epithelial-mesenchymal transition (PubMed: 28651546). Furthermore, it is a key mediator in bone resorption by osteoclasts and serves as a gateway for the entry of pH-dependent viruses into host cells (PubMed: 33053377). While potent inhibitors like bafilomycin A1 and concanamycin A are widely used in research to block ATP6V0C-mediated proton transport, their high toxicity has limited clinical application, prompting the search for more selective or tissue-specific V-ATPase modulators (PubMed: 25635393).

Other names

V-type proton ATPase 16 kDa proteolipid subunitVacuolar proton pump subunit cATP6CATP6LVPPCV-ATPase subunit c

Inhibition of the V0 sector of the V-type ATPase complex, which blocks the translocation of protons across membranes and prevents the acidification of intracellular compartments such as lysosomes and endosomes.