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It features iron-dependent lipid peroxide accumulation accompanied by inadequate redox enzymes, especially glutathione peroxidase 4 (GPX4). RAS-selective lethal 3 (RSL3), erastin, and ferroptosis inducing 56 (FIN56) induce ferroptosis via different manners targeting GPX4 function. Acyl-CoA synthetase long-chain family 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and lipoxygenases (LOXs) participate in the production of lipid peroxides. Heat shock protein family B member 1 (HSPB1) and nuclear receptor coactivator 4 (NCOA4) regulate iron homeostasis preventing ferroptosis caused by the high concentration of intracellular iron. Ferroptosis is ubiquitous in our body as it exists in both physiologic and pathogenic processes. It is involved in glucose-stimulated insulin secretion (GSIS) impairment and arsenic-induced pancreatic damage in the pathogenesis of diabetes. Moreover, iron and the iron-sulfur (Fe-S) cluster influence each other, causing mitochondrial iron accumulation, more reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, failure in biosynthesis of insulin, and ferroptosis in \u03b2-cells. In addition, ferroptosis also engages in the pathogenesis of diabetic complications such as myocardial ischemia and diabetic cardiomyopathy (DCM). In this review, we summarize the mechanism of ferroptosis and especially its association with type 2 diabetes mellitus (T2DM).<\/jats:p>","DOI":"10.1155\/2021\/9999612","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T20:50:26Z","timestamp":1624913426000},"page":"1-10","source":"Crossref","is-referenced-by-count":252,"title":["Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9772-4061","authenticated-orcid":true,"given":"Wenxin","family":"Sha","sequence":"first","affiliation":[{"name":"Diabetes Research Center, School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-8786","authenticated-orcid":true,"given":"Fei","family":"Hu","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, School of Medicine, Ningbo University, Ningbo 315211, China"},{"name":"Cixi Biomedical Research Institute, Wenzhou Medical University, Cixi 315300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5945","authenticated-orcid":true,"given":"Yang","family":"Xi","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1949-216X","authenticated-orcid":true,"given":"Yudong","family":"Chu","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, School of Medicine, Ningbo University, Ningbo 315211, China"},{"name":"Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-6030","authenticated-orcid":true,"given":"Shizhong","family":"Bu","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.033"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7878464"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14186"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2070"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.12.003"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.2174\/1871520611313030007"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00139"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140857"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40907"},{"issue":"2","key":"11","doi-asserted-by":"crossref","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":"B. 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