{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:52:51Z","timestamp":1791543171673,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271455"],"award-info":[{"award-number":["82271455"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The vacuolar ATPase (V\u2010ATPase) is essential for lysosomal acidification and autophagy, and its activity is regulated by nutrient\u2010sensitive reversible assembly of its V1 and Vo domains. While mTORC1 is known to inhibit V\u2010ATPase assembly, the precise molecular mechanisms remain incompletely understood. Here, using TurboID\u2010based proximity labeling and quantitative mass spectrometry, we identified the R2TP complex subunits RPAP3 and PIH1D1 as novel autophagy\u2010responsive interactors of the V\u2010ATPase V1A subunit (encoded by\n                    <jats:italic>ATP6V1A<\/jats:italic>\n                    ). We found that mTORC1 inhibition disrupts the R2TP\u2010V1A interaction, promoting the relocation of the V1 domain to lysosomes and its assembly with the Vo domain to form active proton pumps. Functionally, knockdown of RPAP3 or PIH1D1 enhanced autophagic flux, increased lysosomal proteolytic activity, and promoted the clearance of soluble \u03b1\u2010synuclein in a cellular model of Parkinson's disease (PD). Our study reveals the R2TP complex as a critical molecular switch that couples mTORC1 signaling to V\u2010ATPase assembly and lysosomal function, thereby identifying a new pathway for regulating lysosomal catabolism with significant therapeutic potential for neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.1002\/jcb.70133","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:15:08Z","timestamp":1791540908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The R2TP Complex Couples mTORC1 Signaling to Vacuolar ATPase Assembly and Lysosomal Function"],"prefix":"10.1002","volume":"127","author":[{"given":"Xiao\u2010Wen","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine University of Macau Taipa Macao China"},{"name":"Institute of Chinese Medical Sciences University of Macau Taipa Macao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1285-2378","authenticated-orcid":false,"given":"Ming\u2010Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital (Southwest Hospital) of Third Military Medical University (Army Medical University) Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1855-5568","authenticated-orcid":false,"given":"Qi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Diving and Hyperbaric Medicine, Naval Medical Center Naval Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhuang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine University of Macau Taipa Macao China"},{"name":"Institute of Chinese Medical Sciences University of Macau Taipa Macao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4836-018X","authenticated-orcid":false,"given":"Yu","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine University of Macau Taipa Macao China"},{"name":"Institute of Chinese Medical Sciences University of Macau Taipa Macao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine University of Macau Taipa Macao China"},{"name":"Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, College of Science Southern University of Science and Technology Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-125X","authenticated-orcid":false,"given":"Jia\u2010Hong","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mechanism and Quality of Chinese Medicine University of Macau Taipa Macao China"},{"name":"Institute of Chinese Medical Sciences University of Macau Taipa Macao 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