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• W3208036731 abstract "Itaconic acid is an unsaturated dicarbonic acid. It has a wide range of applications in the industrial production of resins and is also a mediator of immunometabolism in macrophages. Here, we show a previously unrecognized role of itaconic acid in triggering ferroptosis, a form of iron-dependent cell death driven by lipid peroxidation. We found that supraphysiological itaconic acid dose-dependently induces ferroptosis, rather than apoptosis, in human cancer cell lines. Mechanistically, we determined that itaconic acid activates NOCA4-mediated ferritinophagy, which leads to ferroptosis through ferritin degradation and subsequent iron overload and oxidative damage. In contrast, itaconic acid-induced expression and activation of NFE2L2 serves as a defense mechanism to limit ferroptosis by producing antioxidant genes. Consequently, impaired NCOA4 expression prevented, whereas a disrupted NFE2L2 pathway enhanced, sensitivity to itaconic acid-induced ferroptosis in vitro and in xenograft models. These findings establish a dynamic model of metabolite-induced ferroptotic cancer cell death, which may contribute to the development of new targeted therapies." @default.
• W3208036731 created "2021-11-08" @default.
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• W3208036731 date "2021-12-01" @default.
• W3208036731 modified "2023-10-16" @default.
• W3208036731 title "Itaconic acid induces ferroptosis by activating ferritinophagy" @default.
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• W3208036731 doi "https://doi.org/10.1016/j.bbrc.2021.10.054" @default.
• W3208036731 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34735880" @default.
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