{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:32:30Z","timestamp":1785407550414,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Project of Zhejiang Chinese Medical University","award":["701200E003"],"award-info":[{"award-number":["701200E003"]}]},{"name":"Research Project of Zhejiang Chinese Medical University","award":["2024JKZKTS21"],"award-info":[{"award-number":["2024JKZKTS21"]}]},{"name":"Research Project of Zhejiang Chinese Medical University","award":["2025JKZKTS02"],"award-info":[{"award-number":["2025JKZKTS02"]}]},{"award":["701200E003"],"award-info":[{"award-number":["701200E003"]}],"id":[{"id":"https:\/\/ror.org\/04epb4p87","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024JKZKTS21"],"award-info":[{"award-number":["2024JKZKTS21"]}],"id":[{"id":"https:\/\/ror.org\/04epb4p87","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2025JKZKTS02"],"award-info":[{"award-number":["2025JKZKTS02"]}],"id":[{"id":"https:\/\/ror.org\/04epb4p87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>6:2 chlorinated polyfluorinated ether sulfonate (F-53B, also known as 6:2 Cl-PFESA) is a major alternative to perfluorooctane sulfonate (PFOS) and a widespread environmental pollutant with potential public health hazards. However, its nephrotoxic effects and underlying molecular mechanisms remain poorly understood. This study investigated renal injury induced by environmentally relevant concentrations of F-53B and delineated the mechanistic cascade using a mouse model combined with quantitative proteomic and molecular biological approaches. Male C57BL\/6 mice were exposed to 0, 4, 40, and 400 \u03bcg\/L F-53B for 4 weeks. F-53B exposure led to significant renal dysfunction, histopathological damage, elevated renal injury biomarkers, and pronounced oxidative stress in a dose-dependent manner. A proteomic comparison of the 0 \u03bcg\/L versus 400 \u03bcg\/L groups identified 276 differentially expressed proteins that were strongly enriched in oxidative phosphorylation, autophagy, and apoptosis pathways, with cytochrome c oxidase subunit 7b (Cox7b) serving as a core downregulated hub molecule. Further validation confirmed that F-53B triggered overt mitochondrial structural damage, impaired respiratory chain complex assembly, aberrant ATP production, and disturbed mitochondrial dynamics. Consequently, excessive autophagy activation and mitochondrial-mediated apoptosis were simultaneously stimulated in renal tissues. Notably, although statistically significant, the alterations induced by F-53B were generally mild in magnitude. Collectively, our findings demonstrate that F-53B induces nephrotoxicity through a sequential pathological cascade. This study provides novel mechanistic insights into F-53B-elicited renal injury and highlights the potential health risks of this emerging per- and polyfluoroalkyl substance (PFAS) alternative.<\/jats:p>","DOI":"10.3390\/biom16070938","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of F-53B Nephrotoxicity with Oxidative Stress-Mediated Mitochondrial Dysfunction and Altered Autophagy\u2013Apoptosis Crosstalk"],"prefix":"10.3390","volume":"16","author":[{"given":"Bitong","family":"Li","sequence":"first","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongling","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4604-4016","authenticated-orcid":false,"given":"Yaojian","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9686-8298","authenticated-orcid":false,"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-8811","authenticated-orcid":false,"given":"Ran","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8252-3558","authenticated-orcid":false,"given":"Xiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China"},{"name":"Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, 548 Binwen Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.chemosphere.2018.12.186","article-title":"The overlooked short- and ultrashort-chain poly- and perfluorinated substances: A review","volume":"220","author":"Ateia","year":"2019","journal-title":"Chemosphere"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1080\/10934520903139811","article-title":"Perfluoroalkyl sulfonic and carboxylic acids: A critical review of physicochemical properties, levels and patterns in waters and wastewaters, and treatment methods","volume":"44","author":"Rayne","year":"2009","journal-title":"J. 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