{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:46:54Z","timestamp":1785422814142,"version":"3.56.0"},"reference-count":183,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-148508"],"award-info":[{"award-number":["PJT-148508"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review focuses on one of the 16 proteins composing the V-ATPase complex responsible for resorbing bone: the a3 subunit. The rationale for focusing on this biomolecule is that mutations in this one protein account for over 50% of osteopetrosis cases, highlighting its critical role in bone physiology. Despite its essential role in bone remodeling and its involvement in bone diseases, little is known about the way in which this subunit is targeted and regulated within osteoclasts. To this end, this review is broadened to include the three other mammalian paralogues (a1, a2 and a4) and the two yeast orthologs (Vph1p and Stv1p). By examining the literature on all of the paralogues\/orthologs of the V-ATPase a subunit, we hope to provide insight into the molecular mechanisms and future research directions specific to a3. This review starts with an overview on bone, highlighting the role of V-ATPases in osteoclastic bone resorption. We then cover V-ATPases in other location\/functions, highlighting the roles which the four mammalian a subunit paralogues might play in differential targeting and\/or regulation. We review the ways in which the energy of ATP hydrolysis is converted into proton translocation, and go in depth into the diverse role of the a subunit, not only in proton translocation but also in lipid binding, cell signaling and human diseases. Finally, the therapeutic implication of targeting a3 specifically for bone diseases and cancer is discussed, with concluding remarks on future directions.<\/jats:p>","DOI":"10.3390\/ijms22136934","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T11:45:40Z","timestamp":1624880740000},"page":"6934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The V-ATPase a3 Subunit: Structure, Function and Therapeutic Potential of an Essential Biomolecule in Osteoclastic Bone Resorption"],"prefix":"10.3390","volume":"22","author":[{"given":"Anh","family":"Chu","sequence":"first","affiliation":[{"name":"Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A.","family":"Zirngibl","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris F.","family":"Manolson","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3389\/fphar.2020.00757","article-title":"The Bone Extracellular Matrix in Bone Formation and Regeneration","volume":"11","author":"Lin","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10565-019-09510-7","article-title":"Correction to: Role of growth factors in hematopoietic stem cell niche","volume":"36","author":"Lee","year":"2020","journal-title":"Cell Biol. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kitaura, H., Marahleh, A., Ohori, F., Noguchi, T., Shen, W.-R., Qi, J., Nara, Y., Pramusita, A., Kinjo, R., and Mizoguchi, I. (2020). Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145169"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.bone.2016.09.004","article-title":"Visual reporters for study of the osteoblast lineage","volume":"92","author":"Roeder","year":"2016","journal-title":"Bone"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.coph.2016.02.003","article-title":"Osteocytes: The master cells in bone remodelling","volume":"28","author":"Prideaux","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"578477","DOI":"10.3389\/fendo.2020.578477","article-title":"Control of Bone Matrix Properties by Osteocytes","volume":"11","author":"Creecy","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/03008207.2017.1290085","article-title":"Osteoblast-osteoclast interactions","volume":"59","author":"Chen","year":"2018","journal-title":"Connect. Tissue Res."},{"key":"ref_8","first-page":"541","article-title":"Developmental origin, functional maintenance and genetic rescue of osteoclasts","volume":"568","author":"Percin","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41556-019-0437-8","article-title":"Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair","volume":"22","author":"Yahara","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_10","first-page":"8","article-title":"Osteoclast formation at the bone marrow\/bone surface interface: Importance of structural elements, matrix, and intercellular communication","volume":"112","author":"Delaisse","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1146\/annurev-physiol-021119-034425","article-title":"Osteoclasts Provide Coupling Signals to Osteoblast Lineage Cells Through Multiple Mechanisms","volume":"82","author":"Sims","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Takito, J., and Nakamura, M. (2020). Heterogeneity and Actin Cytoskeleton in Osteoclast and Macrophage Multinucleation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186629"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gambari, L., Grassi, F., Roseti, L., Grigolo, B., and Desando, G. (2020). Learning from Monocyte-Macrophage Fusion and Multinucleation: Potential Therapeutic Targets for Osteoporosis and Rheumatoid Arthritis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176001"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Takito, J., Inoue, S., and Nakamura, M. (2018). The Sealing Zone in Osteoclasts: A Self-Organized Structure on the Bone. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040984"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1034\/j.1600-0854.2003.40206.x","article-title":"Osteoclast Ruffled Border Has Distinct Subdomains for Secretion and Degraded Matrix Uptake","volume":"4","author":"Mulari","year":"2003","journal-title":"Traffic"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"22023","DOI":"10.1074\/jbc.M302436200","article-title":"From lysosomes to the plasma membrane: Localization of vacuolar-type H+ -ATPase with the a3 isoform during osteoclast differentiation","volume":"278","author":"Toyomura","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1042\/BST20180445","article-title":"Membrane trafficking in osteoclasts and implications for osteoporosis","volume":"47","author":"Ng","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4068\/cmj.2020.56.2.94","article-title":"Bone Cell Communication Factors Provide a New Therapeutic Strategy for Osteoporosis","volume":"56","author":"Kim","year":"2020","journal-title":"Chonnam. Med. J."},{"key":"ref_19","first-page":"1","article-title":"Friend or Foe? Essential Roles of Osteoclast in Maintaining Skeletal Health","volume":"2020","author":"Wang","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1567-1364.2011.00784.x","article-title":"Dependence of Saccharomyces cerevisiae Golgi functions on V-ATPase activity","volume":"12","author":"Corbacho","year":"2012","journal-title":"FEMS Yeast Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1242\/jeb.172.1.149","article-title":"Structure and function of V-ATPases in endocytic and secretory organelles","volume":"172","author":"Nelson","year":"1992","journal-title":"J. Exp. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1242\/jeb.205.9.1209","article-title":"Characterization of yeast V-ATPase mutants lacking Vph1p or Stv1p and the effect on endocytosis","volume":"205","author":"Perzov","year":"2002","journal-title":"J. Exp. Biol."},{"key":"ref_23","first-page":"19","article-title":"Immunolocalization of the vacuolar-type (H+)-ATPase from clathrin-coated vesicles","volume":"56","author":"Herman","year":"1991","journal-title":"Eur. J. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14166","DOI":"10.1074\/jbc.M114.628891","article-title":"Vacuolar ATPase in Phagosome-Lysosome Fusion","volume":"290","author":"Kissing","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.bbabio.2015.06.010","article-title":"Role of vacuolar-type proton ATPase in signal transduction","volume":"1847","author":"Wada","year":"2015","journal-title":"Biochim. et Biophys. Acta (BBA) Bioenerg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1152\/physrev.00035.2015","article-title":"The Function of V-ATPases in Cancer","volume":"96","author":"Stransky","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/BF00762534","article-title":"Evolution of structure and function of V-ATPases","volume":"24","author":"Kibak","year":"1992","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1023\/A:1025780932403","article-title":"Vacuolar H+ pumping ATPases in luminal acidic organelles and extracellular compartments: Common rotational mechanism and diverse physiological roles","volume":"35","author":"Wada","year":"2003","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1242\/jeb.203.1.107","article-title":"Luminal acidification of diverse organelles by V-ATPase in animal cells","volume":"203","author":"Futai","year":"2000","journal-title":"J. Exp. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1074\/jbc.M117.818872","article-title":"Molecular mechanisms of cutis laxa\u2013 and distal renal tubular acidosis\u2013causing mutations in V-ATPase a subunits, ATP6V0A2 and ATP6V0A4","volume":"293","author":"Esmail","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-physiol-012110-142317","article-title":"Lysosomal Acidification Mechanisms","volume":"74","author":"Mindell","year":"2012","journal-title":"Annu. Rev. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2183\/pjab.95.018","article-title":"Vacuolar-type ATPase: A proton pump to lysosomal trafficking","volume":"95","author":"Futai","year":"2019","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1161\/CIRCRESAHA.115.306799","article-title":"Identification of the (Pro)renin Receptor as a Novel Regulator of Low-Density Lipoprotein MetabolismNovelty and Significance","volume":"118","author":"Lu","year":"2016","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"L270","DOI":"10.1152\/ajplung.00011.2014","article-title":"Suppression of influenza A virus replication in human lung epithelial cells by noncytotoxic concentrations bafilomycin A1","volume":"308","author":"Yeganeh","year":"2015","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/j.1476-5381.2011.01346.x","article-title":"The proton translocation domain of cellular vacuolar ATPase provides a target for the treatment of influenza A virus infections","volume":"164","author":"Saelens","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.2174\/092986707782794005","article-title":"Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases","volume":"14","author":"Jeanjean","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1126\/science.aan6298","article-title":"Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes","volume":"358","author":"Wyant","year":"2017","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.molmed.2012.05.007","article-title":"Amino acids and mTORC1: From lysosomes to disease","volume":"18","author":"Efeyan","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1126\/science.1207056","article-title":"mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H+-ATPase","volume":"334","author":"Zoncu","year":"2011","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27360","DOI":"10.1074\/jbc.M115.659128","article-title":"Amino Acid Availability Modulates Vacuolar H+-ATPase Assembly","volume":"290","author":"Stransky","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1007\/s12035-018-1324-1","article-title":"Chromophore-Assisted Light Inactivation of the V-ATPase V0c Subunit Inhibits Neurotransmitter Release Downstream of Synaptic Vesicle Acidification","volume":"56","author":"Rama","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1007\/s00018-015-1886-2","article-title":"The membrane domain of vacuolar H+ATPase: A crucial player in neurotransmitter exocytotic release","volume":"72","author":"Morel","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0248-4900(03)00075-3","article-title":"Neurotransmitter release: The dark side of the vacuolar-H+ATPase","volume":"95","author":"Morel","year":"2003","journal-title":"Biol. Cell"},{"key":"ref_44","first-page":"23","article-title":"Eukaryotic V-ATPase: Novel structural findings and functional insights","volume":"1837","author":"Marshansky","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.1242\/jcs.03234","article-title":"The a3 isoform of V-ATPase regulates insulin secretion from pancreatic beta-cells","volume":"119","author":"Toyomura","year":"2006","journal-title":"J. Cell. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s10863-005-9482-z","article-title":"Selective Assembly of V-ATPase Subunit Isoforms in Mouse Kidney","volume":"37","author":"Tabata","year":"2005","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1242\/jeb.172.1.231","article-title":"Polarized targeting of V-ATPase in kidney epithelial cells","volume":"172","author":"Brown","year":"1992","journal-title":"J. Exp. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/j.1939-4640.2000.tb03392.x","article-title":"Immunolocalization of CA II and H+ V-ATPase in epithelial cells of the mouse and rat epididymis","volume":"21","author":"Hermo","year":"2000","journal-title":"J. Androl."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1095\/biolreprod.105.043752","article-title":"Distinct Expression Patterns of Different Subunit Isoforms of the V-ATPase in the Rat Epididymis1","volume":"74","author":"Pietrement","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.biocel.2012.05.014","article-title":"V-ATPases in osteoclasts: Structure, function and potential inhibitors of bone resorption","volume":"44","author":"Qin","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/138920312800493179","article-title":"V-ATPase subunit interactions: The long road to therapeutic targeting","volume":"13","author":"Kartner","year":"2012","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s00424-007-0382-4","article-title":"V-ATPase functions in normal and disease processes","volume":"457","author":"Hinton","year":"2009","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/77131","article-title":"Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis","volume":"25","author":"Frattini","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_54","first-page":"22","article-title":"Vacuolar H(+)-ATPase in the kidney","volume":"15","author":"Nakhoul","year":"2002","journal-title":"J. Nephrol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"37476","DOI":"10.1074\/jbc.M110.123281","article-title":"Inhibition of Osteoclast Bone Resorption by Disrupting Vacuolar H+-ATPase a3-B2 Subunit Interaction","volume":"285","author":"Kartner","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1126\/science.2528207","article-title":"Osteoclastic bone resorption by a polarized vacuolar proton pump","volume":"245","author":"Blair","year":"1989","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"902","DOI":"10.3389\/fphys.2018.00902","article-title":"Regulation of V-ATPase Assembly in Nutrient Sensing and Function of V-ATPases in Breast Cancer Metastasis","volume":"9","author":"Collins","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1002\/ijc.27811","article-title":"Inhibitors of vacuolar ATPase proton pumps inhibit human prostate cancer cell invasion and prostate-specific antigen expression and secretion","volume":"132","author":"Michel","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/s41556-018-0219-8","article-title":"TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt\/beta-catenin signalling","volume":"20","author":"Jung","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1083\/jcb.201312109","article-title":"Ca2+-Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via v-ATPase subunit V0a1","volume":"205","author":"Wang","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"eaar1976","DOI":"10.1126\/scisignal.aar1976","article-title":"Lgl reduces endosomal vesicle acidification and Notch signaling by promoting the interaction between Vap33 and the V-ATPase complex","volume":"11","author":"Portela","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1126\/science.aaz2924","article-title":"Structure of V-ATPase from the mammalian brain","volume":"367","author":"Abbas","year":"2020","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1016\/j.bbamcr.2008.06.020","article-title":"Accessory subunit Ac45 controls the V-ATPase in the regulated secretory pathway","volume":"1783","author":"Jansen","year":"2008","journal-title":"Biochim. Biophys. Acta (BBA) Bioenerg."},{"key":"ref_64","first-page":"118","article-title":"Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase","volume":"539","author":"Rohou","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0014-5793(03)00396-X","article-title":"Proton translocation driven by ATP hydrolysis in V-ATPases","volume":"545","author":"Nishi","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"39856","DOI":"10.1074\/jbc.M406767200","article-title":"Topological Characterization of the c, c\u2032, and c\u2033 Subunits of the Vacuolar ATPase from the Yeast Saccharomyces cerevisiae","volume":"279","author":"Flannery","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"34058","DOI":"10.1074\/jbc.M704331200","article-title":"Arrangement of Subunits in the Proteolipid Ring of the V-ATPase","volume":"282","author":"Wang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12397","DOI":"10.1073\/pnas.221291798","article-title":"Arg-735 of the 100-kDa subunit a of the yeast V-ATPase is essential for proton translocation","volume":"98","author":"Nishi","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.15252\/embj.201593447","article-title":"Crystal structure of yeast V1-ATPase in the autoinhibited state","volume":"35","author":"Oot","year":"2016","journal-title":"EMBO J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13831","DOI":"10.1074\/jbc.M200682200","article-title":"The RAVE Complex Is Essential for Stable Assembly of the Yeast V-ATPase","volume":"277","author":"Smardon","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2174\/138920312800493142","article-title":"Targeting Reversible Disassembly as a Mechanism of Controlling V-ATPase Activity","volume":"13","author":"Kane","year":"2012","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10718","DOI":"10.1074\/jbc.RA118.002951","article-title":"MgATP hydrolysis destabilizes the interaction between subunit H and yeast V1-ATPase, highlighting H\u2019s role in V-ATPase regulation by reversible disassembly","volume":"293","author":"Sharma","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"30407","DOI":"10.1074\/jbc.M008768200","article-title":"Interaction between aldolase and vacuolar H+-ATPase: Evidence for direct coupling of glycolysis to the ATP-hydrolyzing proton pump","volume":"276","author":"Lu","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8732","DOI":"10.1074\/jbc.M303871200","article-title":"The Glycolytic Enzyme Aldolase Mediates Assembly, Expression, and Activity of Vacuolar H+-ATPase","volume":"279","author":"Lu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.cmet.2019.05.018","article-title":"Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK","volume":"30","author":"Li","year":"2019","journal-title":"Cell Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"510","DOI":"10.3389\/fcell.2020.00510","article-title":"Regulation of V-ATPase Activity and Organelle pH by Phosphatidylinositol Phosphate Lipids","volume":"8","author":"Banerjee","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1038\/onc.2013.403","article-title":"HRG-1 enhances cancer cell invasive potential and couples glucose metabolism to cytosolic\/extracellular pH gradient regulation by the vacuolar-H+ ATPase","volume":"33","author":"Fogarty","year":"2013","journal-title":"Oncogene"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ceb.2008.03.015","article-title":"The V-type H+-ATPase in vesicular trafficking: Targeting, regulation and function","volume":"20","author":"Marshansky","year":"2008","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10863-007-9116-8","article-title":"The vacuolar (H+)-ATPase: subunit arrangement and in vivo regulation","volume":"39","author":"Qi","year":"2007","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/978-3-319-24780-9_15","article-title":"Function and Regulation of Mammalian V-ATPase Isoforms","volume":"Volume 14","author":"Rahman","year":"2016","journal-title":"Regulation of Ca2+-ATPases, V-ATPases and F-ATPases"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lafourcade, C., Sobo, K., Kieffer-Jaquinod, S., Garin, J., and Van Der Goot, F.G. (2008). Regulation of the V-ATPase along the Endocytic Pathway Occurs through Reversible Subunit Association and Membrane Localization. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002758"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/jcb.26250","article-title":"N-linked glycosylation of a subunit isoforms is critical for vertebrate vacuolar H(+) -ATPase (V-ATPase) biosynthesis","volume":"119","author":"Esmail","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14064","DOI":"10.1016\/S0021-9258(17)36755-8","article-title":"STV1 gene encodes functional homologue of 95-kDa yeast vacuolar H(+)-ATPase subunit Vph1p","volume":"269","author":"Manolson","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jmb.2011.08.051","article-title":"Erratum to \u201cCrystal Structure of the Cytoplasmic N-Terminal Domain of Subunit I, a Homolog of Subunit a, of V-ATPase\u201d [J. Mol. Biol. 412\/1 (2011) 14\u201321]","volume":"413","author":"Srinivasan","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"41908","DOI":"10.1074\/jbc.M308026200","article-title":"Interacting Helical Surfaces of the Transmembrane Segments of Subunits a and c\u2032 of the Yeast V-ATPase Defined by Disulfide-mediated Cross-linking","volume":"278","author":"Nishi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1002\/jbmr.355","article-title":"The V-ATPase a3 subunit mutation R740S is dominant negative and results in osteopetrosis in mice","volume":"26","author":"Ochotny","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"47411","DOI":"10.1074\/jbc.M108310200","article-title":"The Amino-terminal Domain of the Vacuolar Proton-translocating ATPase a Subunit Controls Targeting and in Vivo Dissociation, and the Carboxyl-terminal Domain Affects Coupling of Proton Transport and ATP Hydrolysis","volume":"276","author":"Bowers","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"19487","DOI":"10.1074\/jbc.M112.343814","article-title":"Sorting of the yeast vacuolar-type, proton-translocating ATPase enzyme complex (V-ATPase): Identification of a necessary and sufficient Golgi\/endosomal retention signal in Stv1p","volume":"287","author":"Finnigan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1074\/jbc.M708058200","article-title":"V-ATPase V0 sector subunit a1 in neurons is a target of calmodulin","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1091\/mbc.e11-02-0155","article-title":"Vacuolar H+-ATPase subunits Voa1 and Voa2 cooperatively regulate secretory vesicle acidification, transmitter uptake, and storage","volume":"22","author":"Saw","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-24918-7","article-title":"Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment","volume":"8","author":"Matsumoto","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.bbabio.2014.02.011","article-title":"Diversity of proton pumps in osteoclasts: V-ATPase with a3 and d2 isoforms is a major form in osteoclasts","volume":"1837","author":"Matsumoto","year":"2014","journal-title":"Biochim. et Biophys. Acta (BBA) Bioenerg."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"40050","DOI":"10.1074\/jbc.M106488200","article-title":"a4, a Unique Kidney-specific Isoform of Mouse Vacuolar H+-ATPase Subunit a","volume":"276","author":"Oka","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"11248","DOI":"10.1074\/jbc.RA119.007713","article-title":"Isoform-specific gene disruptions reveal a role for the V-ATPase subunit a4 isoform in the invasiveness of 4T1-12B breast cancer cells","volume":"294","author":"McGuire","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8760","DOI":"10.1074\/jbc.275.12.8760","article-title":"Three subunit a isoforms of mouse vacuolar H(+)-ATPase. Preferential expression of the a3 isoform during osteoclast differentiation","volume":"275","author":"Toyomura","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1093\/hmg\/9.13.2059","article-title":"Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis","volume":"9","author":"Kornak","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"17180","DOI":"10.1002\/jcb.28979","article-title":"Novel c.G630A TCIRG1 mutation causes aberrant splicing resulting in an unusually mild form of autosomal recessive osteopetrosis","volume":"120","author":"Zirngibl","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.7150\/thno.28391","article-title":"V-ATPases and osteoclasts: Ambiguous future of V-ATPases inhibitors in osteoporosis","volume":"8","author":"Duan","year":"2018","journal-title":"Theranostics"},{"key":"ref_99","first-page":"407","article-title":"The Vacuolar Proton ATPase (V-ATPase): Regulation and Therapeutic Targeting","volume":"Volume 14","author":"Chakraborti","year":"2016","journal-title":"Regulation of Ca2+-ATPases, V-ATPases and F-ATPases"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"46396","DOI":"10.1074\/jbc.M303924200","article-title":"Expression and Function of the Mouse V-ATPase d Subunit Isoforms","volume":"278","author":"Nishi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6824","DOI":"10.1074\/jbc.275.10.6824","article-title":"Molecular Cloning and Expression of Three Isoforms of the 100-kDa a Subunit of the Mouse Vacuolar Proton-translocating ATPase","volume":"275","author":"Nishi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/jcb.24434","article-title":"Luteolin inhibition of V-ATPase a3-d2 interaction decreases osteoclast resorptive activity","volume":"114","author":"Crasto","year":"2013","journal-title":"J. Cell Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"C382","DOI":"10.1152\/ajpcell.1996.270.1.C382","article-title":"Osteoclasts express the B2 isoform of vacuolar H(+)-ATPase intracellularly and on their plasma membranes","volume":"270","author":"Lee","year":"1996","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1681\/ASN.2004090761","article-title":"Vacuolar H+-ATPase d2 Subunit: Molecular Characterization, Developmental Regulation, and Localization to Specialized Proton Pumps in Kidney and Bone","volume":"16","author":"Smith","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/nm1514","article-title":"v-ATPase V0 subunit d2\u2013deficient mice exhibit impaired osteoclast fusion and increased bone formation","volume":"12","author":"Lee","year":"2006","journal-title":"Nat. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.kint.2019.09.026","article-title":"Whole exome sequencing identified ATP6V1C2 as a novel candidate gene for recessive distal renal tubular acidosis","volume":"97","author":"Tarsio","year":"2020","journal-title":"Kidney Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-22389-5","article-title":"ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H+-ATPases is essential for brain development in humans and mice","volume":"12","author":"Aoto","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.bone.2018.12.002","article-title":"Sclerosing bone dysplasias with hallmarks of dysosteosclerosis in four patients carrying mutations in SLC29A3 and TCIRG1","volume":"120","author":"Howaldt","year":"2019","journal-title":"Bone"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"354","DOI":"10.4103\/0366-6999.223844","article-title":"Complex Heterozygous Mutation in the T-cell Immune Regulator 1 Gene Associated with Severe Ocular Characteristics of Osteopetrosis in an Infant","volume":"131","author":"Cao","year":"2018","journal-title":"Chin. Med J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1002\/jbmr.2517","article-title":"Buried in the Middle but Guilty: Intronic Mutations in the TCIRG1 Gene Cause Human Autosomal Recessive Osteopetrosis","volume":"30","author":"Palagano","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/jbmr.2203","article-title":"As Little as Needed: The Extraordinary Case of a Mild Recessive Osteopetrosis Owing to a Novel Splicing Hypomorphic Mutation in the TCIRG1 Gene","volume":"29","author":"Sobacchi","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1038\/aps.2017.108","article-title":"Novel mutations of TCIRG1 cause a malignant and mild phenotype of autosomal recessive osteopetrosis (ARO) in four Chinese families","volume":"38","author":"Zhang","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/jbmr.1727","article-title":"The R740S mutation in the V-ATPase a3 subunit increases lysosomal pH, impairs NFATc1 translocation, and decreases in vitro osteoclastogenesis","volume":"28","author":"Voronov","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"26829","DOI":"10.1074\/jbc.M112.345702","article-title":"Osteopetrosis Mutation R444L Causes Endoplasmic Reticulum Retention and Misprocessing of Vacuolar H+-ATPase a3 Subunit","volume":"287","author":"Bhargava","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"26102","DOI":"10.1074\/jbc.M601118200","article-title":"Effects of Human a3 and a4 Mutations That Result in Osteopetrosis and Distal Renal Tubular Acidosis on Yeast V-ATPase Expression and Activity","volume":"281","author":"Ochotny","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"111901","DOI":"10.1016\/j.yexcr.2020.111901","article-title":"V-ATPase a3 isoform mutations identified in osteopetrosis patients abolish its expression and disrupt osteoclast function","volume":"389","author":"Matsumoto","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/jb\/mvaa118","article-title":"Functional complementation of V-ATPase a subunit isoforms in osteoclasts","volume":"169","author":"Matsumoto","year":"2021","journal-title":"J. Biochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"9161","DOI":"10.1074\/jbc.RA119.008552","article-title":"Interaction of the late endo-lysosomal lipid PI(3,5)P2 with the Vph1 isoform of yeast V-ATPase increases its activity and cellular stress tolerance","volume":"294","author":"Banerjee","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1091\/mbc.e17-05-0316","article-title":"Direct interaction of the Golgi V-ATPase a-subunit isoform with PI(4)P drives localization of Golgi V-ATPases in yeast","volume":"28","author":"Banerjee","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"7272","DOI":"10.1073\/pnas.1814818116","article-title":"Structural comparison of the vacuolar and Golgi V-ATPases from Saccharomyces cerevisiae","volume":"116","author":"Vasanthakumar","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"F981","DOI":"10.1152\/ajprenal.00362.2013","article-title":"Regulation of proximal tubule vacuolar H(+)-ATPase by PKA and AMP-activated protein kinase","volume":"306","author":"Gong","year":"2014","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"F943","DOI":"10.1152\/ajprenal.00303.2013","article-title":"AMP-activated protein kinase regulates the vacuolar H+-ATPase via direct phosphorylation of the A subunit (ATP6V1A) in the kidney","volume":"305","author":"Alzamora","year":"2013","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Soliman, M., Seo, J.-Y., Kim, D.-S., Kim, J.-Y., Park, J.-G., Alfajaro, M.M., Baek, Y.-B., Cho, E.-H., Kwon, J., and Choi, J.-S. (2018). Activation of PI3K, Akt, and ERK during early rotavirus infection leads to V-ATPase-dependent endosomal acidification required for uncoating. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006820"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1128\/JVI.01674-18","article-title":"Phosphatidylinositol 3-Kinase\/Akt and MEK\/ERK Signaling Pathways Facilitate Sapovirus Trafficking and Late Endosomal Acidification for Viral Uncoating in LLC-PK Cells","volume":"92","author":"Soliman","year":"2018","journal-title":"J. Virol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1462-5822.2010.01556.x","article-title":"Influenza A virus-induced early activation of ERK and PI3K mediates V-ATPase-dependent intracellular pH change required for fusion","volume":"13","author":"Marjuki","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Roy, M., and Roux, S. (2020). Rab GTPases in Osteoclastic Bone Resorption and Autophagy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207655"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrm2728","article-title":"Rab GTPases as coordinators of vesicle traffic","volume":"10","author":"Stenmark","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1074\/jbc.M112.409169","article-title":"The N termini of a-subunit isoforms are involved in signaling between vacuolar H+-ATPase (V-ATPase) and cytohesin-2","volume":"288","author":"Hosokawa","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.cell.2012.07.032","article-title":"Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1","volume":"150","author":"Schweitzer","year":"2012","journal-title":"Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"9545","DOI":"10.1073\/pnas.1811727115","article-title":"Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms","volume":"115","author":"Shen","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/70563","article-title":"Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification","volume":"23","author":"Li","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/8756-3282(93)90316-3","article-title":"Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis","volume":"14","author":"Bollerslev","year":"1993","journal-title":"Bone"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1359\/jbmr.070109","article-title":"Are Nonresorbing Osteoclasts Sources of Bone Anabolic Activity?","volume":"22","author":"Karsdal","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa031975","article-title":"The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis","volume":"349","author":"Black","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1056\/NEJMoa035725","article-title":"The Effects of Parathyroid Hormone, Alendronate, or Both in Men with Osteoporosis","volume":"349","author":"Finkelstein","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1002\/med.21782","article-title":"Emerging insights on the role of V-ATPase in human diseases: Therapeutic challenges and opportunities","volume":"41","author":"Rodrigues","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"17894","DOI":"10.1074\/jbc.M111.280511","article-title":"Enoxacin Directly Inhibits Osteoclastogenesis without Inducing Apoptosis","volume":"287","author":"Toro","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5144","DOI":"10.1021\/jm900277z","article-title":"Identification of Enoxacin as an Inhibitor of Osteoclast Formation and Bone Resorption by Structure-Based Virtual Screening","volume":"52","author":"Ostrov","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_139","first-page":"3232","article-title":"Bis-enoxacin blocks alveolar bone resorption in rats with ovariectomy-induced osteoporosis","volume":"17","author":"Zhang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1177\/0022034513501876","article-title":"Bis-enoxacin Inhibits Bone Resorption and Orthodontic Tooth Movement","volume":"92","author":"Toro","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1002\/jcb.24489","article-title":"Topology, glycosylation and conformational changes in the membrane domain of the vacuolar H+-ATPase a subunit","volume":"114","author":"Kartner","year":"2013","journal-title":"J. Cell Biochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1002\/1878-0261.12782","article-title":"In vivo anti-V-ATPase antibody treatment delays ovarian tumor growth by increasing anti-tumor immune responses","volume":"14","author":"Kulshrestha","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.18632\/oncotarget.2902","article-title":"Vacuolar ATPase \u2018a2\u2019 isoform exhibits distinct cell surface accumulation and modulates matrix metalloproteinase activity in ovarian cancer","volume":"6","author":"Kulshrestha","year":"2015","journal-title":"Oncotarget"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1016\/j.febslet.2005.07.078","article-title":"Inhibition of the osteoclast V-ATPase by small interfering RNAs","volume":"579","author":"Hu","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Jiang, H., Chen, W., Zhu, G., Zhang, L., Tucker, B., Hao, L., Feng, S., Ci, H., Ma, J., and Wang, L. (2013). RNAi-Mediated Silencing of Atp6i and Atp6i Haploinsufficiency Prevents Both Bone Loss and Inflammation in a Mouse Model of Periodontal Disease. PLOS ONE, 8.","DOI":"10.1371\/journal.pone.0058599"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"32731","DOI":"10.1074\/jbc.M113.503771","article-title":"The Function of Vacuolar ATPase (V-ATPase) a Subunit Isoforms in Invasiveness of MCF10a and MCF10CA1a Human Breast Cancer Cells","volume":"288","author":"Capecci","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1158\/1541-7786.MCR-10-0449","article-title":"The a3 Isoform Vacuolar Type H+-ATPase Promotes Distant Metastasis in the Mouse B16 Melanoma Cells","volume":"9","author":"Nishisho","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"16400","DOI":"10.1074\/jbc.M901201200","article-title":"Function of a Subunit Isoforms of the V-ATPase in pH Homeostasis and in Vitro Invasion of MDA-MB231 Human Breast Cancer Cells","volume":"284","author":"Hinton","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Flinck, M., Hagelund, S., Gorbatenko, A., Severin, M., Pedraz-Cuesta, E., Novak, I., Stock, C., and Pedersen, S.F. (2020). The Vacuolar H+ ATPase \u03b13 Subunit Negatively Regulates Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cells. Cells, 9.","DOI":"10.3390\/cells9020465"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.bone.2018.02.031","article-title":"RNA interference therapy for autosomal dominant osteopetrosis type 2. Towards the preclinical development","volume":"110","author":"Maurizi","year":"2018","journal-title":"Bone"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.1093\/nar\/gkw533","article-title":"Splice-switching antisense oligonucleotides as therapeutic drugs","volume":"44","author":"Havens","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"102581","DOI":"10.1016\/j.ebiom.2019.11.042","article-title":"Multi-cancer V-ATPase molecular signatures: A distinctive balance of subunit C isoforms in esophageal carcinoma","volume":"51","author":"Costa","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1007\/s00198-011-1878-5","article-title":"Autosomal recessive osteopetrosis: Report of 41 novel mutations in the TCIRG1 gene and diagnostic implications","volume":"23","author":"Pangrazio","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e000180","DOI":"10.1136\/bmjophth-2018-000180","article-title":"Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis","volume":"3","author":"Cao","year":"2018","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/jbmr.2100","article-title":"CLCN7andTCIRG1Mutations Differentially Affect Bone Matrix Mineralization in Osteopetrotic Individuals","volume":"29","author":"Barvencik","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/humu.20076","article-title":"TCIRG1-dependent recessive osteopetrosis: Mutation analysis, functional identification of the splicing defects, andin vitro rescue by U1 snRNA","volume":"24","author":"Susani","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1093\/hmg\/10.17.1767","article-title":"The mutational spectrum of human malignant autosomal recessive osteopetrosis","volume":"10","author":"Sobacchi","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/ajh.21447","article-title":"A single-center experience in 20 patients with infantile malignant osteopetrosis","volume":"84","author":"Mazzolari","year":"2009","journal-title":"Am. J. Hematol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1038\/bmt.2016.180","article-title":"Haploidentical transplantation with post-transplant cyclophosphamide following reduced-intensity conditioning for osteopetrosis: Outcomes in three children","volume":"51","author":"Bahr","year":"2016","journal-title":"Bone Marrow Transpl."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00774-010-0228-6","article-title":"Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients","volume":"29","author":"Yuan","year":"2010","journal-title":"J. Bone Miner. Metab."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"108","DOI":"10.29262\/ram.v65i1.314","article-title":"[Identification of new mutations in TCIRG1 as a cause of infantile malignant osteopetrosis in two Mexican patients]","volume":"65","author":"Sobacchi","year":"2018","journal-title":"Rev. Alerg. Mex."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/humu.10165","article-title":"Novel mutations in theTCIRG1gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis","volume":"21","author":"Scimeca","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_163","first-page":"255","article-title":"Autosomal recessive osteopetrosis type I: Description of pathogenic variant of TCIRG1 gene","volume":"75","author":"Sobacchi","year":"2018","journal-title":"Bol. Med. Hosp. Infant. Mex."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/cge.12804","article-title":"The Use of Whole Exome Sequencing for the Diagnosis of Autosomal Recessive Malignant Infantile Osteopetrosis","volume":"92","author":"Shamriz","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Ajmal, M., Mir, A., Wahid, S., Khor, C.C., Foo, J.N., Siddiqi, S., Kauser, M., Malik, S.A., and Nasir, M. (2017). Identification and in silico characterization of a novel p.P208PfsX1 mutation in V-ATPase a3 subunit associated with autosomal recessive osteopetrosis in a Pakistani family. BMC Med Genet., 18.","DOI":"10.1186\/s12881-017-0506-4"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Al-Seraihy, A., Al-Saedi, H., Al-Ahmari, A., Ghemlas, I., and Ayas, M. (2021). T-cell replete haploidentical transplantation with reduced post-transplant cyclophosphamide in six children with infantile osteopetrosis. Bone Marrow Transpl., 1\u20134.","DOI":"10.1038\/s41409-021-01282-1"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejmg.2007.01.005","article-title":"Molecular study of six families originating from the Middle-East and presenting with autosomal recessive osteopetrosis","volume":"50","author":"Souraty","year":"2007","journal-title":"Eur. J. Med. Genet."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3324\/haematol.2019.238261","article-title":"Expanded circulating hematopoietic stem\/progenitor cells as novel cell source for the treatment of TCIRG1 osteopetrosis","volume":"106","author":"Capo","year":"2020","journal-title":"Haematology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0002-9440(10)63798-4","article-title":"Genotype-Phenotype Relationship in Human ATP6i-Dependent Autosomal Recessive Osteopetrosis","volume":"162","author":"Taranta","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1515\/jpem-2013-0007","article-title":"A case of autosomal dominant osteopetrosis type II with a novel TCIRG1 gene mutation","volume":"26","author":"Wada","year":"2013","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"443","DOI":"10.32641\/rchped.v90i4.987","article-title":"Malignant Infantile osteopetrosis","volume":"90","author":"Vomero","year":"2019","journal-title":"Rev. Chil. Pediatr."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/ejhg.2008.234","article-title":"Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: The unique splice site mutation in TCIRG1 gene spread by the founder effect","volume":"17","author":"Bliznetz","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/S8756-3282(01)00684-6","article-title":"Novel mutations in the a3 subunit of vacuolar H+-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis","volume":"30","author":"Michigami","year":"2002","journal-title":"Bone"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.3892\/mmr.2014.1955","article-title":"Identification of TCIRG1 and CLCN7 gene mutations in a patient with autosomal recessive osteopetrosis","volume":"9","author":"Yu","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s12098-013-1250-1","article-title":"Identification of Novel Mutation in Autosomal Recessive Infantile Malignant Osteopetrosis","volume":"81","author":"Siddaiahgari","year":"2013","journal-title":"Indian J. Pediatr."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/jbmr.2929","article-title":"Synonymous Mutations Add a Layer of Complexity in the Diagnosis of Human Osteopetrosis","volume":"32","author":"Palagano","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1136\/jmg.2005.036673","article-title":"Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: Implications for diagnosis and treatment","volume":"43","author":"Peruzzi","year":"2005","journal-title":"J. Med Genet."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2350\/11-05-1032-CR.1","article-title":"A Novel TCIRG1 Gene Mutation Leads to Severe Osteopetrosis with Altered Content of Monocytes\/Macrophages in Several Organs","volume":"15","author":"Gheorghe","year":"2012","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1515\/jpem-2012-0129","article-title":"Infantile malignant osteopetrosis: A rare cause of neonatal hypocalcemia","volume":"25","author":"Engiz","year":"2012","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"101660","DOI":"10.1016\/j.scr.2019.101660","article-title":"Generation of 3 clones of induced pluripotent stem cells (iPSCs) from a patient affected by Autosomal Recessive Osteopetrosis due to mutations in TCIRG1 gene","volume":"42","author":"Lanzi","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.2106\/JBJS.19.00558","article-title":"TCIRG1 Transgenic Rescue of Osteoclast Function Using Induced Pluripotent Stem Cells Derived from Patients with Infantile Malignant Autosomal Recessive Osteopetrosis","volume":"101","author":"Chen","year":"2019","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_182","first-page":"508","article-title":"Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis","volume":"131","author":"Phadke","year":"2010","journal-title":"Indian J. Med Res."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"356","DOI":"10.4274\/jcrpe.2597","article-title":"Genetic Diagnosis Using Whole Exome Analysis in Two Cases with Malignant Osteopetrosis of Infancy","volume":"7","author":"Demir","year":"2015","journal-title":"J. Clin. Res. Pediatr. Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/6934\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:25:40Z","timestamp":1760163940000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/6934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,28]]},"references-count":183,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22136934"],"URL":"https:\/\/doi.org\/10.3390\/ijms22136934","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,28]]}}}