{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T08:54:09Z","timestamp":1769244849275,"version":"3.49.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>We have shown that ABCA1 (ATP-binding cassette protein A1) mediates unfolding of the apoA1 (apolipoprotein A1) N-terminal helical hairpin during apoA1 lipidation. Others have shown that an acidic pH exposes the hydrophobic surface of apoA1. We postulated that the V-ATPase (vacuolar ATPase) proton pump facilitates apoA1 unfolding and promotes ABCA1-mediated cholesterol efflux.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              We found that V-ATPase inhibitors dose-dependently decreased ABCA1-mediated cholesterol efflux to apoA1 in baby hamster kidney cells and RAW264.7 cells; and similarly, siRNA knockdown of ATP6V\n              <jats:sub>0<\/jats:sub>\n              C inhibited ABCA1-mediated cholesterol efflux to apoA1 in RAW264.7 cells. Although ABCA1 expression did not alter total cellular levels of V-ATPase, ABCA1 increased the cell surface levels of the V\n              <jats:sub>0<\/jats:sub>\n              A1 and V\n              <jats:sub>1<\/jats:sub>\n              E1 subunits of V-ATPase. We generated a fluorescein isothiocyanate\/Alexa647 double-labeled fluorescent ratiometric apoA1 pH indicator whose fluorescein isothiocyanate\/Alexa647 emission ratio decreased as the pH drops. We found that ABCA1 induction in baby hamster kidney cells led to acidification of the cell-associated apoA1 pH indicator, compared with control cells without ABCA1 expression. The V-ATPase inhibitor bafilomycin A1 dose-dependently inhibited the apoA1 pH shift in ABCA1-expressing cells, without affecting the levels of cell-associated apoA1. However, we were not able to detect ABCA1-mediated extracellular proton release. We showed that acidic pH facilitated apoA1 unfolding, apoA1 solubilization of phosphatidycholine:phosphatidyserine liposomes, and increased lipid fluidity of these liposomes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our results support a model that ABCA1 recruits V-ATPase to the plasma membrane where V-ATPase mediates apoA1 acidification and membrane remodeling that promote apoA1 unfolding and ABCA1-mediated HDL (high-density lipoprotein) biogenesis and lipid efflux.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311814","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T07:06:39Z","timestamp":1539327999000},"page":"2615-2625","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["V-ATPase (Vacuolar ATPase) Activity Required for ABCA1 (ATP-Binding Cassette Protein A1)-Mediated Cholesterol Efflux"],"prefix":"10.1161","volume":"38","author":[{"given":"Shuhui Wang","family":"Lorkowski","sequence":"first","affiliation":[{"name":"From the Department of Cellular and Molecular Medicine (S.W.L., G.B., K.G., J.D.S.), Cleveland Clinic, OH."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Brubaker","sequence":"additional","affiliation":[{"name":"From the Department of Cellular and Molecular Medicine (S.W.L., G.B., K.G., J.D.S.), Cleveland Clinic, OH."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kailash","family":"Gulshan","sequence":"additional","affiliation":[{"name":"From the Department of Cellular and Molecular Medicine (S.W.L., G.B., K.G., J.D.S.), Cleveland Clinic, OH."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan D.","family":"Smith","sequence":"additional","affiliation":[{"name":"From the Department of Cellular and Molecular Medicine (S.W.L., G.B., K.G., J.D.S.), Cleveland Clinic, OH."},{"name":"Department of Cardiovascular Medicine (J.D.S.), Cleveland Clinic, OH."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.79.1.8"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2013.08.001"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60312-2"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.20.9607"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117412"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.301195"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1187"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M200279-JLR200"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308856"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm729"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/70563"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.203.1.137"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.4.2005"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-07-0559"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800287-JLR200"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M028118"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.173815"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300078-JLR200"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi700079w"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002790"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000201042.00725.84"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11358"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103264200"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M314160200"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707720200"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2008.01261.x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2272"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.19.11290"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.21.3923"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.10.023"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-08-0685"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(94)90166-X"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000237920.70451.ad"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800597-JLR200"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-016-1796-7"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.02014"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107938200"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300336-JLR200"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709597200"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01250"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.238063"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.118.311814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:50:19Z","timestamp":1715554219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.118.311814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1161\/ATVBAHA.118.311814"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.118.311814","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"2017-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}