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Research progress on the role of HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis

ZHOU Jie, LI Fang^*, ZHU Xue-Yu, SHEN Hai-Jun, LU Rong-Zhu

Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang 212013, China

Abstract

Hypoxia-inducible factors (HIFs) are one of the primary transcription factors regulating oxygen balance, and their stability is determined by the hydroxylation state of the prolyl hydroxylase domain (PHD) that is sensitive to oxygen. In recent years, studies have shown that HIFs-prolyl hydroxylases (PHDs) oxygen-sensing pathway is involved in the process of cellular ferroptosis. Ferroptosis, a new type of cell death, different from necrosis, apoptosis, necrotizing apoptosis, and pyroptosis, is essentially a programmed death caused by the accumulation of iron-dependent lipid peroxides in cells. This paper focuses on the role and mechanism of the HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis involved in nerve diseases, tumors, lung injury, and chemical nerve damage from three aspects of iron metabolism, lipid metabolism, and glutathione (GSH) synthesis/metabolism. This review will provide a theoretical basis and new ideas for the development of novel drugs targeting the HIFs-PHDs oxygen-sensing pathway and capable of regulating ferroptosis for the treatment of diseases related to ferroptosis such as nervous system diseases and tumors.

Key words: hypoxia-inducible factors; prolyl hydroxylase; ferroptosis; iron metabolism; lipid reactive oxygen species

Received: 2020-12-28　　Accepted: 2021-06-03

Corresponding author: 李芳　　E-mail: lfsjy@ujs.edu.cn

Citing This Article：

ZHOU Jie, LI Fang, ZHU Xue-Yu, SHEN Hai-Jun, LU Rong-Zhu. Research progress on the role of HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis. Acta Physiol Sin 2021; 73 (6): 1017-1024 (in Chinese with English abstract).