{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:07:00Z","timestamp":1782396420944,"version":"3.54.5"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Shanghai Natural Science Foundation","doi-asserted-by":"crossref","award":["23ZR1459600"],"award-info":[{"award-number":["23ZR1459600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Disciplines in the Three-Year Plan of the Shanghai Municipal Public Health System","award":["GWVI-11.1-41 and 42"],"award-info":[{"award-number":["GWVI-11.1-41 and 42"]}]},{"name":"Key Projects in the Three-Year Plan of the Shanghai Municipal Public Health System","award":["GWVI-4"],"award-info":[{"award-number":["GWVI-4"]}]},{"name":"Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Safety Evaluation\/National Key Laboratory of Environmental and Health Impact Assessment of New Pollutants"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Bisphenol AF (BPAF) is a prevalent environmental contaminant with demonstrated metabolic and immunological toxicity. This study aimed to investigate whether VDAC1 (Voltage-Dependent Anion Channel 1) mediates BPAF-induced succinate dysmetabolism and inflammatory responses in macrophages, and to evaluate the therapeutic potential of VDAC1 silencing. Methods: RAW264.7 macrophages were exposed to BPAF (0\u20132500 nM, 24 h) with or without VDAC1 siRNA transfection. Succinate levels, SDH activity, mitochondrial function (complexes I\u2013V, ATP, membrane potential), and inflammatory markers (TNF-\u03b1, IL-6, IL-1\u03b2, ROS, MDA) were quantified. A 90-day oral toxicity study in C57BL\/6J mice (0\u201332 mg kg\u22121) assessed systemic inflammation and hepatic ultrastructure. p38 MAPK\/NF-\u03baB signaling was evaluated by Western blot and immunofluorescence. Results: BPAF elevated succinate 2.3-fold and decreased SDH activity by 48%, coinciding with reduced mitochondrial membrane potential and ATP synthesis (p &lt; 0.01). Inflammatory cytokines and ROS were markedly increased. VDAC1 siRNA reversed these perturbations, restored complex II activity, and blunted p38 MAPK\/NF-\u03baB activation. In vivo, BPAF dose-dependently increased serum TNF-\u03b1, IL-6 and IL-1\u03b2, promoted NF-\u03baB nuclear translocation and mitochondrial swelling, without altering body or liver weight; VDAC1 knockdown mitigated these effects. Conclusions: VDAC1 orchestrates BPAF-elicited succinate accumulation and macrophage inflammation via p38 MAPK\/NF-\u03baB signaling. Targeted VDAC1 silencing alleviates metabolic and inflammatory injury, offering a promising therapeutic strategy against BPAF-related diseases.<\/jats:p>","DOI":"10.3390\/ph18111600","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["VDAC1 Intervention Alleviates Bisphenol AF-Induced Succinate Metabolism Dysregulation and Inflammatory Responses"],"prefix":"10.3390","volume":"18","author":[{"given":"Xinyu","family":"Hong","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5330-2218","authenticated-orcid":false,"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Leng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelei","family":"Qian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonghua","family":"Tao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental and Health Impact Assessment of New Pollutants, Institute of Chemical Safety Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1289\/ehp.0901819","article-title":"Bisphenol AF is a full agonist for the estrogen receptor ER\u03b1 but a highly specific antagonist for ER\u03b2","volume":"118","author":"Matsushima","year":"2010","journal-title":"Environ. 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