Mechanisms and regulations of ferroptosis

Front Immunol. 2023 Oct 6:14:1269451. doi: 10.3389/fimmu.2023.1269451. eCollection 2023.

Abstract

Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body's primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.

Keywords: autophagy; ferroptosis; iron metabolism; lipid metabolism; lipid peroxidation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Ferroptosis*
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Humans
  • Iron / metabolism
  • Iron Overload*
  • Lipid Peroxidation / physiology
  • Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism

Substances

  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Iron
  • Glutathione Peroxidase
  • Antioxidants
  • Glutathione

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This manuscript was supported by 2022 Henan Province Medical Science and Technology Joint Construction Project (LHGJ20220317), 2023 Provincial Natural Science Foundation Project of Henan Province (232300420038), 2023 Provincial Natural Science Foundation Youth Fund Project of Henan Province (232300420249) and The present study was supported by The Key Scientific Research Project Plan of Henan University (Grant No.20A320037) and 2022 Henan Province Key R&D and Promotion Special Support Project (The role of OSBP2 in the regulation of malignant phenotype of pancreatic cancer).