{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:57:24Z","timestamp":1790791044947,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"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":["82472488"],"award-info":[{"award-number":["82472488"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intervertebral disc degeneration (IVDD) is an age\u2010related disease accompanied by disrupted mitochondrial homeostasis and defective autophagy. Cellular senescence induces ion imbalance, which leads to mitochondrial damage and suppressed autophagic flux; nevertheless, the molecular mechanism underlying this process remains poorly understood. Here, by integrating single\u2010cell RNA sequencing (single\u2010cell RNA\u2010seq), messenger RNA sequencing (mRNA\u2010seq), and liquid chromatography\u2010mass spectrometry (LC\u2010MS), we identified zinc transporter ZIP14 (SLC39A14) as a critical regulatory factor. Further investigations revealed that deacetylation at lysine 302 (K302) of annexin A2 (ANXA2) serves as a core intracellular zinc\u2010dependent regulatory node controlling mitophagy. In vitro site\u2010directed mutagenesis combined with molecular dynamics simulations demonstrated that acetylation at the ANXA2 K302 residue alters the conformation and function of the ANXA2\u2010mTOR complex. Specifically, K302 acetylation enhances the interaction between ANXA2 and mTOR, consequently restraining cellular mitophagy. Mechanistically, zinc\u2010dependent modification of ANXA2 governs mTOR activity, bridging disturbed ion homeostasis and autophagy machinery. We also characterized the intracellular degradation pattern of ANXA2 and clarified its abnormal accumulation during IVDD development. In vivo experiments verified that ZIP14 (SLC39A14) is required to maintain intracellular Zn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    levels and sustain ANXA2\u2010mTOR signaling. Consistently, dietary zinc supplementation effectively slows IVDD progression, highlighting a potential therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1002\/advs.77870","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Persistent Zn\n                    <sup>2+<\/sup>\n                    Influx\u2010Mediated Deacetylation of ANXA2 Regulates the \u201cZn\n                    <sup>2+<\/sup>\n                    \u2010Autophagic Flux\u201d and Alleviates Intervertebral Disc Degeneration"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6776-1341","authenticated-orcid":false,"given":"Yuxin","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Zhejiang\u2010Hong Kong Joint Laboratory for Precision Diagnosis and Treatment of Spinal Diseases Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3862-4933","authenticated-orcid":false,"given":"Yongcheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Zhejiang\u2010Hong Kong Joint Laboratory for Precision Diagnosis and Treatment of Spinal Diseases Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5919-0875","authenticated-orcid":false,"given":"Yihao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Zhejiang\u2010Hong Kong Joint Laboratory for Precision Diagnosis and Treatment of Spinal Diseases Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Zhejiang\u2010Hong Kong Joint Laboratory for Precision Diagnosis and Treatment of Spinal Diseases Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhui","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Zhejiang\u2010Hong Kong Joint Laboratory for Precision Diagnosis and Treatment of Spinal Diseases Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7837-9392","authenticated-orcid":false,"given":"Zhihua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Zhejiang\u2010Hong Kong Joint Laboratory for Precision Diagnosis and Treatment of Spinal Diseases Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-5055","authenticated-orcid":false,"given":"Minhao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Zhejiang\u2010Hong Kong Joint Laboratory for Precision Diagnosis and Treatment of Spinal Diseases Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0206-2167","authenticated-orcid":false,"given":"Qizhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinic of Spine Center Xinhua Hospital Shanghai Jiaotong University School of Medicine  Shanghai P. R. 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