ATPase H+ transporting V0 subunit c (ATP6V0C)

The Vacuolar-type H+-ATPase (V-ATPase) Vo c-subunit is a fundamental component of the V-ATPase enzyme complex, a multi-subunit molecular motor that functions as an ATP-dependent proton pump (GeneCards, https://www.genecards.org/cgi-bin/cardprep.pl?gene=ATP6V0C). Encoded by the ATP6V0C gene, this 16 kDa proteolipid forms a rotating ring within the membrane-embedded V0 domain, which is responsible for translocating protons across biological membranes to acidify intracellular organelles like lysosomes and endosomes (NIH, https://pmc.ncbi.nlm.nih.gov/articles/PMC2852119/). This acidification is crucial for diverse cellular processes, including protein degradation, receptor-mediated endocytosis, and nutrient sensing via the mTOR pathway (NIH, https://pmc.ncbi.nlm.nih.gov/articles/PMC7674343/). In disease states, the c-subunit is often overexpressed in cancer cells to promote an acidic microenvironment conducive to invasion and metastasis, and it plays a key role in bone resorption by osteoclasts in osteoporosis (NIH, https://pmc.ncbi.nlm.nih.gov/articles/PMC5726535/). Mutations in ATP6V0C have been linked to neurodevelopmental disorders, including epilepsy and intellectual disability, highlighting its importance in neuronal function (MDPI, https://www.mdpi.com/2073-4409/12/11/1519; Brain, https://academic.oup.com/brain/article/146/4/1431/6692484). While potent inhibitors like bafilomycin A1 and concanamycin A target the c-subunit to block proton transport, their high systemic toxicity has challenged the development of clinically viable therapeutics, leading to ongoing research into more selective V-ATPase modulators (ResearchGate, https://www.researchgate.net/publication/343014433_Cryo-EM_structure_of_bafilomycin_A1_bound_intact_bovine_V-ATPase).

Other names

ATP6LV-ATPase 16 kDa proteolipid subunitVacuolar proton pump 16 kDa proteolipid subunitVPPCEPEO3ATPase lysosomal 16kDa subunit 1

Inhibition of the V-ATPase proton pump by binding to the c-subunit ring in the V0 domain, thereby blocking the rotation required for proton translocation and preventing the acidification of intracellular and extracellular compartments (NIH, https://pmc.ncbi.nlm.nih.gov/articles/PMC2852119/; ResearchGate, https://www.researchgate.net/publication/343014433_Cryo-EM_structure_of_bafilomycin_A1_bound_intact_bovine_V-ATPase).