BIOCHEMICAL MECHANISMS OF FERROPTOSIS

DOI: https://doi.org/10.29296/24999490-2023-02-03

A.A. Nikolaev
Astrakhan State Medical University, Ministry of Health of the Russian Federation,
Bakinskaya st., 121, Astrakhan, 414000, Russian Federation

The review is devoted to the analysis of modern ideas about the molecular mechanisms of the development of ferroptosis; the main conditions for the development of this type of cell death are described, and cell markers and targets for the induction of ferroptosis are characterized. The aim of the study was to determine the current state of the issue and characterize the molecular markers of the induction of a decrease in the activity of glutathione peroxidase 4 (GPX4), lipid peroxidation caused by hyperproduction of ROS by excess iron-containing components. Material and methods: the analysis and systematization of scientific literature over the past 10 years was carried out in the PubMed, Scopus and Google Scholar databases. Results: The review focuses on two cellular components whose inhibition causes ferroptotic death: the cystine/glutamate antiporter xCT system and GPX4. This review describes in detail the disorders of iron metabolism. Iron can directly generate excess ROS through the Fenton reaction, thereby increasing oxidative damage. In addition, iron can increase the activity of lipoxygenase. In conclusion, attention is drawn to the unresolved issues of the mechanism of ferroptosis and the prospects for the induction and inhibition of ferroptosis for therapeutic purposes.
Keywords: 
ferroptosis, iron metabolism, glutathione peroxidase-4, ferritin, transferrin, ferroportin

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