{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:46:01Z","timestamp":1790444761830,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Gliomas are the predominant form of malignant brain tumors. We investigated the mechanism of hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) affecting glioma metabolic reprogramming, proliferation and invasion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human glioma cell U87 was cultured under hypoxia and treated with small interfering (si)HIF\u20101\u03b1, si\u2010B cell lymphoma\u20102\/adenovirus E1B 19\u2010kDa interacting protein 3 (siBNIP3), si\u2010YT521\u2010B homology domain 2 (siYTHDF2), 3\u2010methyladenine and 2\u2010deoxyglucose, with exogenous sodium lactate\u2010treated normally\u2010cultured cells as a lactate\u2010positive control. Cellular hexokinase 2, lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 enzyme activities, glucose uptake, and levels of lactic acid and adenosine triphosphate (ATP), and HIF\u20101\u03b1, glycolysis\u2010related proteins, mitophagy\u2010related proteins, histone H3 lysine 18 lactylation (H3K18la) and YTHDF2 were determined by ELISA, 2\u2010NBDG, kits, and Western blot. Extracellular acidification rate (ECAR), and cell proliferation, invasion, apoptosis and mitophagy were evaluated by extracellular flux analysis, CCK\u20108, Transwell, flow cytometry, and immunofluorescence staining. H3K18la\u2010YTHDF2 relationship and YTHDF2\u2010BNIP3 interaction were assessed by ChIP and Co\u2010IP assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hypoxia\u2010induced highly\u2010expressed HIF\u20101\u03b1 in glioma cells increased glycolysis\u2010related protein levels, glycolytic enzyme activities, glucose uptake, lactic acid production, ATP level and ECAR, thereby promoting metabolic reprogramming, invasion and proliferation. HIF\u20101\u03b1 mediated metabolic reprogramming, proliferation and invasion through BNIP3\u2010dependent mitophagy, which were partly negated by mitophagy inhibition. HIF\u20101\u03b1 induced histone Kla modification to upregulate YTHDF2. YTHDF2 downregulation impeded YTHDF2\u2010BNIP3 interaction and inhibited HIF\u20101\u03b1\u2010induced BNIP3\u2010dependent mitophagy, curbing glioma cell metabolic reprogramming, proliferation and invasion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Hypoxia\u2010induced high HIF\u20101\u03b1 expression upregulated YTHDF2 through hH3K18la modification, enhanced YTHDF2\u2010BNIP3 interaction, and regulated BNIP3\u2010dependent mitophagy\u2010mediated metabolic reprogramming to affect glioma proliferation and invasion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70069","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:40:09Z","timestamp":1737348009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hypoxia\u2010Inducible Factor\u20101\u03b1 Regulates BNIP3\u2010Dependent Mitophagy and Mediates Metabolic Reprogramming Through Histone Lysine Lactylation Modification to Affect Glioma Proliferation and Invasion"],"prefix":"10.1002","volume":"39","author":[{"given":"Feng","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory the First Affiliated Hospital of Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichang","family":"Yin","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Immunology Qiqihar University Qiqihar China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1117-7934","authenticated-orcid":false,"given":"Zhixing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery the First Affiliated Hospital of Harbin Medical University Harbin 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