{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:59:25Z","timestamp":1790899165755,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"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":["82230020"],"award-info":[{"award-number":["82230020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430026"],"award-info":[{"award-number":["82430026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82500828"],"award-info":[{"award-number":["82500828"]}],"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>Acute kidney injury (AKI) is a clinical syndrome associated with severe morbidity and high mortality, for which there are no currently effective therapies. Aging, a state associated with Klotho protein decline, is an independent risk factor for AKI development and progression. Here, we report that Klotho\u2010derived peptide 1 (KP1), a small peptide that recapitulates the renoprotective potential of Klotho, effectively protects against AKI in mouse models induced by either cisplatin or ischemia\u2010reperfusion injury. KP1 treatment improved kidney function, ameliorated structural damage, inhibited tubular cell apoptosis, and preserved mitochondrial integrity in both models. Mechanistically, KP1 entered kidney proximal tubular epithelial cells via endocytosis, directly targeted the mitochondrial protein ATPase family AAA domain\u2010containing protein 3A (ATAD3A), and prevented its degradation,\u00a0and preserved its function. By interacting with the hypoxia inducible gene 1 (HIG1) domain family member 2A (HIGD2A) and maintaining its expression and function within the mitochondria, ATAD3A prevented cytochrome c release and inhibited caspase activation following injury, thereby alleviating renal tubular cell apoptosis. Collectively, these studies demonstrate that KP1 is a promising therapeutic agent for AKI by directly targeting and preserving mitochondrial integrity. Our findings also lay the groundwork for developing novel therapeutic strategies to treat diseases associated with mitochondrial dysfunction.<\/jats:p>","DOI":"10.1002\/advs.77214","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:17:10Z","timestamp":1787663830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Klotho\u2010Derived Peptide 1 Protects against Acute Kidney Injury by Directly Targeting Mitochondrial ATAD3A"],"prefix":"10.1002","author":[{"given":"Xiaoyao","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment National Clinical Research Center for Kidney and Urological Diseases Division of Nephrology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research Guangdong Provincial Institute of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0032-2346","authenticated-orcid":false,"given":"Shihui","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment National Clinical Research Center for Kidney and Urological Diseases Division of Nephrology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research Guangdong Provincial Institute of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment National Clinical Research Center for Kidney and Urological Diseases Division of Nephrology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research Guangdong Provincial Institute of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment National Clinical Research Center for Kidney and Urological Diseases Division of Nephrology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research Guangdong Provincial Institute of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment National Clinical Research Center for Kidney and Urological Diseases Division of Nephrology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research Guangdong Provincial Institute of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3742-8886","authenticated-orcid":false,"given":"Xue","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment National Clinical Research Center for Kidney and Urological Diseases Division of Nephrology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research Guangdong Provincial Institute of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-805X","authenticated-orcid":false,"given":"Youhua","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment National Clinical Research Center for Kidney and Urological Diseases Division of Nephrology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research Guangdong Provincial Institute of Nephrology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32563\u20102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010025\u201001030\u20104"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00284-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-020-04849-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-020-00369-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0004832022"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u201003152\u2010y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.113741"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00285.2020"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010026\u201001072\u20102"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02840320"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.328"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.11.023"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020239"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.56082"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015040446"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00504.2019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800751R"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28096-z"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.89105"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20100716\u20100954\u20105"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2026.01.018"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.10.040"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-024-05473-z"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00240\u2010025\u201001734\u2010z"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14696"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.49690"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512511"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210730119"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00007\u201010"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00766-z"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1997052"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21217917"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp7114"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12953\u2010020\u201000160\u2010w"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2012\u20101159"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107607"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA120.002076"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122620"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28362"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010389"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.01.026"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.162060"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.96233"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77214","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77214","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:17:11Z","timestamp":1787663831000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":44,"alternative-id":["10.1002\/advs.77214"],"URL":"https:\/\/doi.org\/10.1002\/advs.77214","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"assertion":[{"value":"2026-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77214"}}