{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:00:18Z","timestamp":1782986418526,"version":"3.54.5"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Rifampicin is the most common pathogenic factor in anti\u2010tuberculosis drug\u2010induced liver injury (AT\u2010DILI), the mechanisms that it promotes hepatocyte damage in AT\u2010DILI are not yet to be thoroughly elucidated. In this study, we investigated the potential molecular mechanisms for ferroptosis involving rifampicin hepatotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Animal and cell injury models of rifampicin were constructed, and the toxicity of rifampicin was assessed by physicochemical staining and cell viability assay. Next, flow cytometry was employed to detect changes in ferroptosis\u2010related markers, and Western blotting was used to detect protein expression. Then, the important role of autophagy and ferroptosis was verified with small molecule compound intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that ferritinophagy\u2010induced ferroptosis participates in the toxicity of rifampicin, and the mechanism is that rifampicin precisely activates high\u2010throughput autophagy, which leads to the massive degradation of ferritin and the increase of free iron. Moreover, rifampicin exhibited conspicuous inhibition of Human 71\u2009kDa heat shock cognate protein (HSPA8) that is intimately associated with Microtubule\u2010associated protein light chain 3 isoform B (LC3B) expression, in turn, HSPA8 inducer attenuated intracellular autophagy flux. Of note, inducing HSPA8 or inhibition of autophagy and ferroptosis considerably relieved the hepatotoxicity of rifampicin in mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study highlights the crucial roles of the HSPA8 and autophagy in ferroptotic cell death driving by rifampicin, particularly illumines multiple promising regulatory nodes for therapeutic interventions in diseases involving AT\u2010DILI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15459","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T08:54:45Z","timestamp":1666083285000},"page":"2889-2899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Inhibition of <scp>HSPA8<\/scp> by rifampicin contributes to ferroptosis via enhancing autophagy"],"prefix":"10.1111","volume":"42","author":[{"given":"Juan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University  Zhuzhou Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzheng","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University  Zhuzhou Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University  Zhuzhou Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhuzhou 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