Molekulyarnaya Meditsina (Molecular medicine)Molekulyarnaya Meditsina (Molecular medicine)Молекулярная медицина1728-29182499-9490Russkiy Vrach Publishing House34081610.29296/24999490-2023-02-03ReviewsОбзорыReview ArticleBiochemical mechanisms of ferroptosisБиохимические механизмы ферроптозаhttps://orcid.org/0000-0001-6607-430XNikolaevAlexander A.НиколаевАлександр Аркадьевич
Russian Federation

Head of the Department of Chemistry, Doctor of Medical Sciences, Professor

зав. кафедрой химии, доктор медицинских наук, профессор

chimnik@mail.ruAstrakhan State Medical University, Ministry of Health of the Russian FederationФГБОУ ВО «Астраханский государственный медицинский университет» Минздрава РФ2104202321219241804202318042023Copyright ©; 2023, Russkiy Vrach Publishing HouseCopyright ©; 2023, ИД "Русский врач"2023Russkiy Vrach Publishing HouseИД "Русский врач"https://journals.eco-vector.com/1728-2918/article/view/340816

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.

Обзор посвящен анализу современных представлений о молекулярных механизмах развития ферроптоза; описаны основные условия развития этого вида клеточной смерти и охарактеризованы клеточные маркеры и мишени индукции ферроптоза.

Целью исследования было определить современное состояние вопроса и охарактеризовать молекулярные маркеры индукции снижения активности глутатионпероксидазы 4 (GPX4), перекисного окисления липидов, вызванного гиперпродукцией АФК избыточными железосодержащими компонентами.

Материал и методы: анализ и систематизация научной литературы за последние 10 лет выполнены в базах данных PubMed, Scopus и Google Scholar.

Результаты: особое внимание в обзоре уделено двум клеточных компонентам, ингибирование которых вызывает ферроптотическую гибель: системе xCT цистин/глутамат антипортер и GPX4. В данном обзоре детально охарактеризованы нарушения метаболизма железа. Железо может напрямую генерировать избыточное количество АФК посредством реакции Фентона, тем самым увеличивая окислительное повреждение. Кроме того, железо может повышать активность липоксигеназы. Обращается внимание на нерешенные вопросы механизма ферроптоза и перспективы индукции и ингибирования ферроптоза в терапевтических целях.

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