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Review
. 2024 Mar 18:11:1329147.
doi: 10.3389/fcell.2023.1329147. eCollection 2023.

Understanding the unique mechanism of ferroptosis: a promising therapeutic target

Yuanyuan Kong  1 , Jing Li  2 , Rufeng Lin  1 , Shifeng Lu  1 , Liucheng Rong  1 , Yao Xue  1 , Yongjun Fang  1
Affiliations
Review

Understanding the unique mechanism of ferroptosis: a promising therapeutic target

Yuanyuan Kong et al. Front Cell Dev Biol. .

Abstract

Ferroptosis is an iron-dependent form of regulated cell death and is characterized by high concentrations of intracellular lipid peroxide and a redox imbalance in the cells. Ferroptosis shows distinct morphological and biological features compared with other prominent mechanisms of programmed cell death. The distinct characteristics of ferroptosis include the dysfunction of the lipid peroxide repair enzyme glutathione peroxidase 4, the presence of ferrous iron overload, and the lipid peroxidation of polyunsaturated fatty acids. Several other metabolic pathways (including iron, lipid, and amino acid metabolism) and ferritinophagy, as well as transcription factors, can modulate ferroptosis. However, to date, the molecular mechanism of ferroptosis has not been elucidated. This review outlines the discovery, characterization, regulatory mechanisms, and crosstalk of ferroptosis. Further, we have noted the controversial elements in the ferroptosis-related mechanisms. Our inferences may provide a partial reference for developing strategies to regulate ferroptosis.

Keywords: GPX4; cell death; ferroptosis; iron metabolism; reactive oxygen species.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The discovery of ferroptosis.
FIGURE 2
FIGURE 2
Iron metabolism (right) and GSH/GPX4 (left) pathway diagram.
FIGURE 3
FIGURE 3
The signal pathway of lipid peroxidation.
FIGURE 4
FIGURE 4
The association between ferroptosis and clinical diseases.
See this image and copyright information in PMC

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