Modern representations about signaling pathways and protective mechanisms of ferroptosis. A biological role of diffusion of death signals of ferroptotic cells

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Abstract

Ferroptosis as the type nonapoptosis adjustable destruction of cells arises and develops by means of difficult signals and regulatory mechanisms. The reactive oxygen species (ROS) used to initiate ferroptosis come from a variety of sources, including iron-mediated Fenton reactions, mitochondrial ROS, and membrane-associated ROS driven by the NOX protein family. Polyunsaturated fatty acid-containing phospholipids are the main substrates of lipid peroxidation in ferroptosis, which is positively regulated by enzymes, such as ACSL4, LPCAT3, ALOXs, or POR. Selective activation of autophagic degradation pathways promotes ferroptosis by increasing iron accumulation to cause lipid peroxidation. In contrast, system Xc–-glutathione–GPX4 axis plays a central role in limiting lipid peroxidation, although other antioxidants (such as coenzyme Q10 and tetrahydrobiopterin) can also inhibit ferroptosis. A main nuclear mechanism of cell defense against ferroptosis is the activation of the NFE2L2-dependent antioxidant response by transcriptionally upregulating the expression of antioxidants or cytoprotective genes. Additionally, the membrane damage caused by ferroptotic stimulus can be repaired by ESCRT-III-dependent membrane scission machinery. In this review, we summarize recent progress in understanding the signaling pathways and defense mechanisms of ferroptosis.

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About the authors

Vladimir I. Vashchenko

Kirov Military Medical Academy

Author for correspondence.
Email: vladimir-vaschenko@yandex.ru

Dr. Sci. (Biol.), leading research associate, Сentre of Blood and Tissues

Russian Federation, Saint Petersburg

Elena F. Sorocoletova

Kirov Military Medical Academy

Email: helensoroc@yandex.ru

Cans. Sci. (Med.), senior research associate, the Research Centre

Russian Federation, Saint Petersburg

Petr D. Shabanov

Kirov Military Medical Academy

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477

professor and head of the S.V. Anichkov Department of Neuropharmacology

Russian Federation, Saint Petersburg

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