Vacuolar H+-ATPase c-ring (V-ATPase c-ring) (V-ATPase c-ring)

The Vacuolar H+-ATPase (V-ATPase) c-ring is a membrane-embedded rotary component of the V-ATPase holoenzyme, a multi-subunit proton pump responsible for acidifying intracellular compartments and the extracellular environment (Forgac, 2007; Nishi and Forgac, 2002). Composed of multiple proteolipid subunits (primarily subunit c, encoded by ATP6V0C), the c-ring rotates relative to the 'a' subunit to translocate protons across the lipid bilayer, driven by ATP hydrolysis in the cytosolic V1 domain (Inoue et al., 2005). This acidification is vital for lysosomal function, protein sorting, and the entry of various pathogens such as influenza and Ebola viruses (Marshansky et al., 2008). In cancer, the c-ring is frequently upregulated and localized to the plasma membrane, where it acidifies the tumor microenvironment to facilitate extracellular matrix degradation, metastasis, and drug resistance (Sennoune et al., 2004; Lu and Qin, 2011). It also plays a pivotal role in bone resorption by osteoclasts, making it a target for treating osteoporosis (Gordon & Drum, 1994). While potent inhibitors like bafilomycins and archazolids target the c-ring to block proton transport, their clinical utility is currently limited by systemic toxicity due to the essential housekeeping roles of V-ATPases in all eukaryotic cells (Huss and Wieczorek, 2009).

Other names

V-ATPase proteolipid ringV0 c-ringVacuolar proton pump c-ringATP6V0C ring16 kDa proteolipid ring

Inhibition of the V0 domain rotation and blocking of the proton-conducting pore within the proteolipid c-ring, thereby preventing ATP-driven proton translocation across membranes (Forgac, 2007; Huss and Wieczorek, 2009).