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Although iron is necessary for metabolic homeostasis, it induces a programmed necrosis. Iron release from ferritin storage is through nuclear receptor coactivator 4 (NCOA4)-mediated autophagic degradation, known as ferritinophagy. However, the role of ferritinophagy in the stressed heart remains unclear. Deletion of\n                    <jats:italic>Ncoa4<\/jats:italic>\n                    in mouse hearts reduced left ventricular chamber size and improved cardiac function along with the attenuation of the upregulation of ferritinophagy-mediated ferritin degradation 4 weeks after pressure overload. Free ferrous iron overload and increased lipid peroxidation were suppressed in NCOA4-deficient hearts. A potent inhibitor of lipid peroxidation, ferrostatin-1, significantly mitigated the development of pressure overload-induced dilated cardiomyopathy in wild-type mice. Thus, the activation of ferritinophagy results in the development of heart failure, whereas inhibition of this process protects the heart against hemodynamic stress.\n                  <\/jats:p>","DOI":"10.7554\/elife.62174","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T19:00:27Z","timestamp":1611601227000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62174","source":"Crossref","is-referenced-by-count":136,"title":["Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5149-9962","authenticated-orcid":true,"given":"Jumpei","family":"Ito","sequence":"first","affiliation":[{"name":"The School of Cardiovascular Medicine and Sciences, King\u2019s College London British Heart Foundation Centre of Excellence, London, United Kingdom"},{"name":"Department of Pharmacology, Faculty of Medicine, Osaka 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