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Review
. 2022 May;477(5):1453-1461.
doi: 10.1007/s11010-021-04327-7. Epub 2022 Feb 15.

The role of ferroptosis in acute lung injury

Xin Liu  1 , Junqiang Zhang  2   3 , Wang Xie  4
Affiliations
Review

The role of ferroptosis in acute lung injury

Xin Liu et al. Mol Cell Biochem. 2022 May.

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common disease with high morbidity and mortality, and its pathogenesis is believed to be related to oxidative stress, apoptosis, inflammation, and hypoxia. Ferroptosis is a type of nonapoptotic cell death characterized by iron-dependent lipid peroxide accumulation and is involved in many cellular physiological processes. Recent studies have confirmed that ferroptosis may be involved in the development of ALI. This review summarizes the most recent discoveries on the role of ferroptosis in ALI to provide new strategies for its prevention and treatment.

Keywords: Acute lung injury; Ferroptosis; Glutathione peroxidase 4; Lipid peroxidation.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Mechanism and regulation of ferroptosis in alveolar epithelial cells in ALI. In alveolar epithelial cells, pathogenic factors can increase the levels of Fe3+ and H2O2. Increased Fe3+ can be reduced to Fe2+ by Steap3 and then enter the cytoplasm via DMT1 to generate free radicals through the Fenton reaction. These free radicals can oxidize membrane lipids, such as PUFAs, into lipid peroxides, constantly disrupting the structure and function of cell biofilms, thus inducing ferroptosis and leading to ALI. This process can be inhibited by regulating key proteins of the ferroptosis pathway, such as GPX4 and System XC, as well as the labile iron pool. System XC− cystine/glutamate antiporter system; PUFA polyunsaturated fatty acid; GSH glutathione; GSSG glutathione disulfide; GPX4 glutathione peroxidase 4; Fpn ferroportin; TFR1 transferrin receptor 1; STEAP3 six-transmembrane epithelial antigen of the prostate 3; LIP labile iron pool; ROS reactive oxygen species; DFO deferoxamine; CPX ciclopirox; HMOX1 heme oxygenase 1; BSO buthionine sulfoximine; DAMPS damage-associated molecular patterns; ALI acute lung injury
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