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ALKBH5 induces ferroptosis in the HH\/R model by mutating the 3\u2032\u2010UTR of G3BP1 mRNA and m<jats:sup>6<\/jats:sup>A sites at positions 142 and 173. Mutations of sites 142 and 173 only partially affect the levels of p53<jats:sup>N\/T<\/jats:sup>, SLC7A11 and ferroptosis. G3BP1, YBX1 and p53 protein can bind to each other, and p53 can inhibit the expression of SLC7A11 via nuclear binding to the promoter region of SLC7A11 mRNA. The p53 and YBX1 proteins can synergistically enter the nucleus to aggravate cell damage, while G3BP1 is expressed in the cytoplasm and inhibits p53 binding to SLC7A11 by blocking the entry of the p53 and YBX1 proteins into the nucleus. ALKBH5 promotes G3BP1 expression through m<jats:sup>6<\/jats:sup>A methylation at m<jats:sup>6<\/jats:sup>A sites 142 and 173. Subsequently, G3BP1, YBX1, and p53 interact with each other, the amount of synergistic nuclear translocation of YBX1 and p53 is reduced, and the level of p53 nuclear translocation that inhibiting SLC7A11 transcription is decreased, thereby inhibits cardiomyocyte ferroptosis and reducing myocardial tissue damage during myocardial IRI in diabetes.<\/jats:p>","DOI":"10.1002\/advs.202507254","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T09:55:23Z","timestamp":1750672523000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["ALKBH5\u2010Mediated M<sup>6<\/sup>A Demethylation of G3BP1 Attenuates Ferroptosis Via Cytoplasmic Retention of YBX1\/p53 in Diabetic Myocardial Ischemia\u2010Reperfusion Injury"],"prefix":"10.1002","volume":"12","author":[{"given":"Wenyuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  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