Mitochondrial Ferritin Is a Hypoxia-Inducible Factor 1α-Inducible Gene That Protects from Hypoxia-Induced Cell Death in Brain

作者：Qiong Wu, Wen-Shuang Wu, Lin Su, Xin Zheng, Wenyue Wu, Paolo Santambrogio, Yu-Jing Gou, Hao Qian, Pei-Na Wang, Ya-Ru Li, Bao-Lu Zhao, Guangjun Nie, Sonia Levi, Yan-Zhong Chang · 发表于：Antioxidants and Redox Signaling · 年份：2018 · DOI：10.1089/ars.2017.7063 · 被引用次数：60 · 研究领域：Autophagy in Disease and Therapy、RNA modifications and cancer、Heme Oxygenase-1 and Carbon Monoxide

Aims: Mitochondrial ferritin (protein [FtMt]) is preferentially expressed in cell types of high metabolic activity and oxygen consumption, which is consistent with its role of sequestering iron and preventing oxygen-derived redox damage. As of yet, the mechanisms of FtMt regulation and the protection FtMt affords remain largely unknown. Results: Here, we report that hypoxia-inducible factor 1α (HIF-1α) can upregulate FtMt expression. We verify one functional hypoxia-response element (HRE) in the positive regulatory region and two HREs possessing HIF-1α binding activity in the minimal promoter region of the human FTMT gene. We also demonstrate that FtMt can alleviate hypoxia-induced brain cell death by sequestering uncommitted iron, whose levels increase with hypoxia in these cells. Innovation: In the absence of FtMt, this catalytic metal excess catalyzes the production of cytotoxic reactive oxygen species. Conclusion: Thus, the cell ability to increase expression of FtMt during hypoxia may be a skill to avoid tissue damage derived from oxygen limitation.