{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:48:42Z","timestamp":1792842522502,"version":"4.5.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Ferroptosis is a new type of cell death caused by the lack of glutathione peroxidase 4 (GPX4) and the imbalance of cellular redox. It is characterized by the accumulation of lipid peroxides on cell membranes. Multiple regulatory pathways of ferroptosis include the GPX4, glutamate-cystine antiporter (System Xc<jats:sup>\u2013<\/jats:sup>), lipid metabolism, and iron metabolism pathways. Recent studies have reported that autophagy-dependent ferroptosis (ferroptosis meditated by ferritinophagy, lipophagy, and clockophagy) plays a significant role in the occurrence of several diseases, including diseases affecting the nerves, liver, lungs, and kidneys. This review provides an overview of research progress made on autophagy-dependent ferroptosis in kidney diseases.<\/jats:p>","DOI":"10.3389\/fmed.2022.1071864","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T04:52:41Z","timestamp":1674449561000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Autophagy-dependent ferroptosis in kidney disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Yuanting","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.ceb.2009.12.003","article-title":"Necroptosis as an alternative form of programmed cell death.","volume":"22","author":"Christofferson","year":"2010","journal-title":"Curr Opin Cell Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrmicro2070","article-title":"Pyroptosis: host cell death and inflammation.","volume":"7","author":"Bergsbaken","year":"2009","journal-title":"Nat Rev Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death.","volume":"149","author":"Dixon Scott","year":"2012","journal-title":"Cell."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e2716","DOI":"10.1038\/cddis.2017.133","article-title":"Mitochondrial complex i inhibition triggers a mitophagy-dependent ros increase leading to necroptosis and ferroptosis in melanoma cells.","volume":"8","author":"Basit","year":"2017","journal-title":"Cell Death Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s41419-022-04628-9","article-title":"Targeting ferroptosis in acute kidney injury.","volume":"13","author":"Ni","year":"2022","journal-title":"Cell Death Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tcb.2015.10.014","article-title":"Ferroptosis: death by lipid peroxidation.","volume":"26","author":"Yang","year":"2016","journal-title":"Trends Cell Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"E4966","DOI":"10.1073\/pnas.1603244113","article-title":"Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis.","volume":"113","author":"Yang","year":"2016","journal-title":"Proc Natl Acad Sci USA."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1021\/acschembio.5b00245","article-title":"Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death.","volume":"10","author":"Dixon","year":"2015","journal-title":"ACS Chem Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e2006203","DOI":"10.1371\/journal.pbio.2006203","article-title":"Unsolved mysteries: how does lipid peroxidation cause ferroptosis?","volume":"16","author":"Feng","year":"2018","journal-title":"PLoS Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.21037\/tgh.2019.11.15","article-title":"Inherited iron overload disorders.","volume":"5","author":"Piperno","year":"2020","journal-title":"Transl Gastroenterol Hepatol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.chembiol.2008.02.010","article-title":"Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-ras-harboring cancer cells.","volume":"15","author":"Yang","year":"2008","journal-title":"Chem Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/nature05859","article-title":"Ras-Raf-Mek-dependent oxidative cell death involving voltage-dependent anion channels.","volume":"447","author":"Yagoda","year":"2007","journal-title":"Nature."},{"key":"B13","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1080\/15548627.2016.1187366","article-title":"Autophagy promotes ferroptosis by degradation of ferritin.","volume":"12","author":"Hou","year":"2016","journal-title":"Autophagy."},{"key":"B14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy.","volume":"24","author":"Feng","year":"2014","journal-title":"Cell Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e132826","DOI":"10.1172\/jci.insight.132826","article-title":"Mitophagy-dependent macrophage reprogramming protects against kidney fibrosis.","volume":"4","author":"Bhatia","year":"2019","journal-title":"JCI Insight."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1007\/s00018-011-0865-5","article-title":"Microautophagy: lesser-known self-eating.","volume":"69","author":"Li","year":"2012","journal-title":"Cell Mol Life Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.semcdb.2010.02.005","article-title":"Chaperone-mediated autophagy: molecular mechanisms and physiological relevance.","volume":"21","author":"Orenstein","year":"2010","journal-title":"Semin Cell Dev Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s40139-017-0139-5","article-title":"Autophagy and ferroptosis\u2014what is the connection?","volume":"5","author":"Kang","year":"2017","journal-title":"Curr Pathobiol Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/bs.mcb.2020.10.012","article-title":"Monitoring autophagy-dependent ferroptosis.","volume":"165","author":"Li","year":"2021","journal-title":"Methods Cell Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e10308","DOI":"10.7554\/eLife.10308","article-title":"Ferritinophagy via ncoa4 is required for erythropoiesis and is regulated by iron dependent herc2-mediated proteolysis.","volume":"4","author":"Mancias","year":"2015","journal-title":"eLife."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1016\/j.biopha.2018.11.030","article-title":"Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway.","volume":"109","author":"Kong","year":"2019","journal-title":"Biomed Pharmacother."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1080\/15548627.2018.1503146","article-title":"Activation of ferritinophagy is required for the Rna-binding protein Elavl1\/Hur to regulate ferroptosis in hepatic stellate cells.","volume":"14","author":"Zhang","year":"2018","journal-title":"Autophagy."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1038\/s41467-019-10991-7","article-title":"Involvement of cigarette smoke-induced epithelial cell ferroptosis in copd pathogenesis.","volume":"10","author":"Yoshida","year":"2019","journal-title":"Nat Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/cdd.2012.63","article-title":"Regulation of lipid stores and metabolism by lipophagy.","volume":"20","author":"Liu","year":"2013","journal-title":"Cell Death Differ."},{"key":"B25","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease.","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1002\/hep.27667","article-title":"The small gtpase Rab7 as a central regulator of hepatocellular lipophagy.","volume":"61","author":"Schroeder","year":"2015","journal-title":"Hepatology."},{"key":"B27","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.bbrc.2018.12.039","article-title":"Lipid storage and lipophagy regulates ferroptosis.","volume":"508","author":"Bai","year":"2019","journal-title":"Biochem Biophys Res Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.1016\/j.jmb.2020.04.003","article-title":"Molecular links between the circadian clock and the cell cycle.","volume":"432","author":"Farshadi","year":"2020","journal-title":"J Mol Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.tcb.2013.07.002","article-title":"Molecular architecture of the mammalian circadian clock.","volume":"24","author":"Partch","year":"2014","journal-title":"Trends Cell Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"eaaw2238","DOI":"10.1126\/sciadv.aaw2238","article-title":"Clockophagy is a novel selective autophagy process favoring ferroptosis.","volume":"5","author":"Yang","year":"2019","journal-title":"Sci Adv."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1016\/j.cub.2018.05.094","article-title":"Ampk-mediated becn1 phosphorylation promotes ferroptosis by directly blocking system Xc(\u2013) activity.","volume":"28","author":"Song","year":"2018","journal-title":"Curr Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1073\/pnas.1819728116","article-title":"Chaperone-mediated autophagy is involved in the execution of ferroptosis.","volume":"116","author":"Wu","year":"2019","journal-title":"Proc Natl Acad Sci USA."},{"key":"B33","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by Gpx4.","volume":"156","author":"Yang","year":"2014","journal-title":"Cell."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.3389\/fphar.2018.01371","article-title":"Rsl3 drives ferroptosis through Gpx4 inactivation and ros production in colorectal cancer.","volume":"9","author":"Sui","year":"2018","journal-title":"Front Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40880-018-0288-x","article-title":"Amino acid transporter Slc7a11\/Xct at the crossroads of regulating redox homeostasis and nutrient dependency of cancer.","volume":"38","author":"Koppula","year":"2018","journal-title":"Cancer Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e02523","DOI":"10.7554\/eLife.02523","article-title":"Pharmacological inhibition of cystine\u2013glutamate exchange induces endoplasmic reticulum stress and ferroptosis.","volume":"3","author":"Dixon","year":"2014","journal-title":"eLife."},{"key":"B37","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/s41401-020-0478-3","article-title":"Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma.","volume":"42","author":"Li","year":"2021","journal-title":"Acta Pharmacol Sin."},{"key":"B38","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"Acsl4 dictates ferroptosis sensitivity by shaping cellular lipid composition.","volume":"13","author":"Doll","year":"2017","journal-title":"Nat Chem Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nature13148","article-title":"Quantitative proteomics identifies Ncoa4 as the cargo receptor mediating ferritinophagy.","volume":"509","author":"Mancias","year":"2014","journal-title":"Nature."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1).","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1001\/jama.2019.14745","article-title":"Chronic kidney disease diagnosis and management: a review.","volume":"322","author":"Chen","year":"2019","journal-title":"JAMA."},{"key":"B42","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1159\/000517723","article-title":"Targeting ferroptosis attenuates interstitial inflammation and kidney fibrosis.","volume":"8","author":"Zhou","year":"2022","journal-title":"Kidney Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"112892","DOI":"10.1016\/j.fct.2022.112892","article-title":"Umbelliferone delays the progression of diabetic nephropathy by inhibiting ferroptosis through activation of the Nrf-2\/Ho-1 pathway.","volume":"163","author":"Jin","year":"2022","journal-title":"Food Chem Toxicol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41420-022-00931-8","article-title":"Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5\/6 nephrectomy-induced Ckd rat model.","volume":"8","author":"Wang","year":"2022","journal-title":"Cell Death Discov."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1016\/s0140-6736(19)32563-2","article-title":"Acute kidney injury.","volume":"394","author":"Ronco","year":"2019","journal-title":"Lancet."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1080\/15548627.2020.1848971","article-title":"Inhibiting Nlrp3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of Hif1a and Bnip3-mediated mitophagy.","volume":"17","author":"Lin","year":"2020","journal-title":"Autophagy."},{"key":"B47","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.kint.2019.02.009","article-title":"Regulated necrosis in kidney ischemia-reperfusion injury.","volume":"96","author":"Pefanis","year":"2019","journal-title":"Kidney Int."},{"key":"B48","doi-asserted-by":"publisher","first-page":"101254","DOI":"10.1016\/j.redox.2019.101254","article-title":"Pink1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial Ros and Nlrp3 inflammasome activation.","volume":"26","author":"Lin","year":"2019","journal-title":"Redox Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1681\/asn.2015121376","article-title":"Ferroptosis, but not necroptosis, is important in nephrotoxic folic acid\u2013induced aki.","volume":"28","author":"Martin-Sanchez","year":"2017","journal-title":"J Am Soc Nephrol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41419-020-2256-z","article-title":"Vdr activation attenuate cisplatin induced aki by inhibiting ferroptosis.","volume":"11","author":"Hu","year":"2020","journal-title":"Cell Death Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41419-020-03362-4","article-title":"Legumain promotes tubular ferroptosis by facilitating chaperone-mediated autophagy of Gpx4 in aki.","volume":"12","author":"Chen","year":"2021","journal-title":"Cell Death Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"6203","DOI":"10.1111\/jcmm.16567","article-title":"Cirbp promotes ferroptosis by interacting with elavl1 and activating ferritinophagy during renal ischaemia-reperfusion injury.","volume":"25","author":"Sui","year":"2021","journal-title":"J Cell Mol Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/s41585-020-0362-4","article-title":"Epidemiology, definition and treatment of complicated urinary tract infections.","volume":"17","author":"Wagenlehner","year":"2020","journal-title":"Nat Rev Urol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1093\/cid\/cit284","article-title":"Urinary tract infections: current and emerging management strategies.","volume":"57","author":"Barber","year":"2013","journal-title":"Clin Infect Dis."},{"key":"B55","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1080\/15548627.2016.1160176","article-title":"Ferritinophagy drives uropathogenic Escherichia Coli persistence in bladder epithelial cells.","volume":"12","author":"Bauckman","year":"2016","journal-title":"Autophagy."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1158\/2159-8290.Cd-19-0499","article-title":"Tumor microenvironment dynamics in clear-cell renal cell carcinoma.","volume":"9","author":"Vuong","year":"2019","journal-title":"Cancer Discov."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1038\/s41467-019-09277-9","article-title":"A Gpx4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis.","volume":"10","author":"Zou","year":"2019","journal-title":"Nat Commun."},{"key":"B58","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12885-020-07726-z","article-title":"Low expression of ferritinophagy-related ncoa4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma.","volume":"21","author":"Mou","year":"2021","journal-title":"BMC Cancer."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1071864\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T04:52:45Z","timestamp":1674449565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1071864\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":58,"alternative-id":["10.3389\/fmed.2022.1071864"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.1071864","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,23]]},"article-number":"1071864"}}