{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATP6V0C, the c subunit of the vacuolar H⁺-ATPase (V-ATPase) complex, is essential for proton translocation and the acidification of intracellular compartments, particularly lysosomes. This acidification underpins multiple cellular processes including the regulation of autophagic flux, mTOR signaling, and intracellular pH homeostasis. Disruption of ATP6V0C function–for example, by siRNA‐mediated knockdown–impairs lysosomal acidification, leads to the accumulation of autophagy substrates, and increases sensitivity to pharmacological stressors, thereby exacerbating cell death or neurological dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer cells, ATP6V0C modulates intracellular pH, contributing to chemoresistance by facilitating the sequestration of weak-base chemotherapeutic agents into acidic endo-lysosomal compartments. Moreover, interactions between ATP6V0C and tumor metastasis suppressor proteins such as LASS2/TMSG1 regulate V-ATPase activity and thereby influence cancer cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n ATP6V0C is also a key host factor in infectious disease. It is targeted by viral microRNAs during human cytomegalovirus infection and is manipulated by viral accessory proteins such as HIV-1 Vpu, which affects tetherin degradation to promote viral release. In addition, bacterial effectors like VepA interact directly with ATP6V0C to induce lysosomal membrane permeabilization and subsequent host cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in metabolic contexts such as high-glucose conditions, downregulation of ATP6V0C disrupts the autophagy-lysosome pathway in gingival epithelial cells, contributing to inflammatory responses, while genetic alterations in ATP6V0C have been linked to neurodevelopmental disorders including epilepsy and intellectual disability. Collectively, these findings underscore the multifaceted role of ATP6V0C in regulating lysosomal function, cellular metabolism, pathogen defense, and disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Leandra R Mangieri, Burton J Mader, Cailin E Thomas, et al. 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