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Review
. 2017 Apr;21(4):648-657.
doi: 10.1111/jcmm.13008. Epub 2016 Nov 10.

Ferroptosis, a new form of cell death, and its relationships with tumourous diseases

Haitao Yu  1 , Pengyi Guo  1 , Xiaozai Xie  1 , Yi Wang  2 , Gang Chen  1
Affiliations
Review

Ferroptosis, a new form of cell death, and its relationships with tumourous diseases

Haitao Yu et al. J Cell Mol Med. 2017 Apr.

Abstract

Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis and results from iron-dependent lipid peroxide accumulation. Ferroptotic cell death is characterized by cytological changes, including cell volume shrinkage and increased mitochondrial membrane density. Ferroptosis can be induced by two classes of small-molecule substances known as class 1 (system Xc- inhibitors) and class 2 ferroptosis inducers [glutathione peroxidase 4 (GPx4) inhibitors]. In addition to these small-molecule substances, a number of drugs (e. g. sorafenib, artemisinin and its derivatives) can induce ferroptosis. Various factors, such as the mevalonate (MVA) and sulphur-transfer pathways, play pivotal roles in the regulation of ferroptosis. Ferroptosis plays an unneglectable role in regulating the growth and proliferation of some types of tumour cells, such as lymphocytoma, ductal cell cancer of the pancreas, renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Here, we will first introduce the discovery of and research pertaining to ferroptosis; then summarize the induction mechanisms and regulatory pathways of ferroptosis; and finally, further elucidate the roles of ferroptosis in human tumourous diseases VSports手机版. .

Keywords: erastin; ferroptosis; iron-dependent cell death; tumourous diseases. V体育安卓版.

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Figures

Figure 1
Figure 1
The occurrence and regulatory mechanisms of ferroptosis in a cell. Ferroptosis inducers such as erastin, sorafenib and sulfasalazine inhibit SLC7A11 insystemXc − andimpede the uptake of cystine by cells, thus leading to a decline in intracellular cysteine and a subsequent reduction in glutathione (GSH), which requires cysteine for its synthesis; this ultimately results in declination of anti‐oxidative ability of cells. Through the sulphur‐transfer pathways, cellular methionine can be used to supplement the cysteine level. As a key component in ferroptosis, GPx4 can bind with GSH and suppress cellular lipid peroxides to prevent cellular ferroptosis. Class 2 ferroptosis inducers such as RSL3 can directly suppress GPx4 to induce ferroptosis. The MVA pathway plays an important role in regulating GPx4 maturation. Iron, which is indispensable to ferroptosis, can be transported from outside to the inside of the cells by transferrin. Ironchelators can impede ferroptosis. Mitochondria are the most important organelle involved in ferroptosis; they contain six ferroptosis‐related genes and release ferroptosis‐inducing lipid peroxides through the electron transport chain. In addition, a number of intracellular molecules/proteinscan regulate ferroptosis;e.g. P53 inhibits SLC7A11 and promotes the production of lipid peroxides. HSPB1 can inhibit ferroptosis by impeding the increase in intracellular iron. Some anti‐oxidants, such as vitamin E, liproxstain‐1 and ubiquinone (Co Q10), can impede ferroptosis by directly suppressing lipid peroxides.
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