Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan; Center for Low-temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Sydney Medical School, The University of Sydney, NSW, Australia.
Arch Biochem Biophys. 2020 Aug 15;689:108440. doi: 10.1016/j.abb.2020.108440. Epub 2020 May 30.
Iron is essential for all the lives on earth but may trigger a switch toward ferroptosis, a novel form of regulated necrosis. Carbonic anhydrases (CAs) are ubiquitous enzymes from microbes to humans. The primary function of CAs is to regulate cellular pH by hydrating carbon dioxide (CO) to protons (H) and bicarbonate ions (HCO). Furthermore, CAs play roles in biosynthetic reactions, such as gluconeogenesis, lipogenesis, ureagenesis and are also associated with tumor metabolism, suggesting that CAs may be a potential target for the treatment of cancers. We have recently revealed a novel function of CA IX in ferroptosis-resistance by using human malignant mesothelioma cells. Herein, we aim to review the potential molecular association between ferroptosis and CAs, from the viewpoint of iron-metabolism, lipogenesis and signaling pathways both under physiological and pathological contexts.
铁对于地球上所有生物都是必不可少的，但它也可能引发向铁死亡的转变，这是一种新的细胞程序性死亡形式。碳酸酐酶（CA）是从微生物到人类中无处不在的酶。CA 的主要功能是通过将二氧化碳（CO）水合为质子（H）和碳酸氢根离子（HCO）来调节细胞 pH 值。此外，CA 在生物合成反应中发挥作用，如糖异生、脂肪生成、尿素生成，并且还与肿瘤代谢有关，这表明 CA 可能是癌症治疗的潜在靶点。我们最近通过使用人类恶性间皮瘤细胞揭示了 CAIX 在铁死亡抵抗中的新功能。在此，我们旨在从生理和病理环境下的铁代谢、脂肪生成和信号通路的角度，综述铁死亡与 CA 之间潜在的分子关联。
