{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T06:33:39Z","timestamp":1792996419177,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"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":["82400401"],"award-info":[{"award-number":["82400401"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mitophagy is essential for mitochondrial quality control during myocardial ischemia\u2013reperfusion (I\/R) injury. Lysosomal protein transmembrane 5 (LAPTM5) has been implicated in cardiovascular disease and autophagy, but its role in cardiac mitophagy remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LAPTM5 knockout mice and cardiomyocyte\u2010targeted AAV9\u2010cTnT\u2010LAPTM5 were used to determine the role of LAPTM5 in myocardial I\/R injury. Cardiomyocyte hypoxia\/reoxygenation models, mt\u2010Keima imaging, mitochondrial fractionation, LC3\u2010mitochondrial colocalization, co\u2010immunoprecipitation, molecular docking, site\u2010directed mutagenesis, NEDD4 gain\u2010 and loss\u2010of\u2010function, and p62 ubiquitination assays were used to investigate the underlying mechanism. Depending on data distribution and group number, appropriate parametric or non\u2010parametric statistics were applied together with correction for multiple testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LAPTM5 expression progressively decreased following I\/R or H\/R stress. LAPTM5 deficiency aggravated myocardial injury, cardiac dysfunction, and mitochondrial structural and functional damage, whereas LAPTM5 overexpression attenuated these abnormalities. LAPTM5 promoted mitophagy by enhancing LC3 recruitment to mitochondria. Mechanistically, LAPTM5 recruited NEDD4 to mitochondria through its PY3 motif and facilitated NEDD4\u2010LC3 complex formation. NEDD4 depletion abolished LAPTM5\u2010mediated mitophagy and cytoprotection, whereas re\u2010expression of NEDD4\u2010WT, but not the E3\u2010inactive NEDD4\u2010CS mutant, restored these effects. NEDD4\u2010WT also increased p62 ubiquitination. AAV9\u2010mediated LAPTM5 re\u2010expression reduced infarct size, improved cardiac function, and preserved mitochondrial integrity in LAPTM5\u2010deficient hearts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LAPTM5 protects against myocardial I\/R injury by promoting mitophagy through the NEDD4\u2010LC3 axis. PY3\u2010dependent recruitment of NEDD4 and its E3 ubiquitin ligase activity facilitate LC3\u2010associated mitochondrial clearance, accompanied by enhanced p62 ubiquitination, thereby preserving mitochondrial homeostasis during reperfusion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70876","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:23:49Z","timestamp":1792643029000},"source":"Crossref","is-referenced-by-count":0,"title":["Lysosomal protein transmembrane 5 protects against myocardial ischemia\u2010reperfusion injury by promoting mitophagy via the NEDD4\u2010LC3 axis"],"prefix":"10.1002","volume":"16","author":[{"given":"Yadan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan P. R. China"},{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan P. R. China"},{"name":"Taikang Center for Life and Medical Sciences Taikang Medical School Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7475-5014","authenticated-orcid":false,"given":"Qingqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan P. R. China"},{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan P. R. China"},{"name":"Taikang Center for Life and Medical Sciences Taikang Medical School Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan P. R. China"},{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan P. R. China"},{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan P. R. China"},{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-3169","authenticated-orcid":false,"given":"Qizhu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan P. R. China"},{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases  Wuhan P. R. China"},{"name":"Taikang Center for Life and Medical Sciences Taikang Medical School Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.08.015"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.11.007"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)30677\u20108"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.316306"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2024.02.056"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.203"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010022\u201000542\u20102"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010023\u201000676\u2010x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010024\u201001060\u20102"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010025\u201000873\u2010w"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0364"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200603001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.04.024"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000371"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2205629119"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.355917"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2110428119"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2117893"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2026097"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1268301"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201007303\u20103"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010023\u201001019\u20109"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.740526"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039159\u20100"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14170"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155658"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010024\u201001042\u20104"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065603"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.02.012"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201045044\u20101"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010022\u201000703\u2010y"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.03.004"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010023\u201001009\u2010x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.263408"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010026\u201008654\u20109"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70331"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.22\u20100008"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201060207\u20104"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201029660\u20103"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3186"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001503\u20107"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010026\u201001012\u20109"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010026\u201002813\u20102"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010025\u201001203\u20107"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012\u2010024\u201009916\u20108"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70876","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ctm2.70876","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70876","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T05:39:44Z","timestamp":1792993184000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/ctm2.70876"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70876","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"article-number":"e70876"}}