Mechanism of Ferroptosis and Its Role in Spinal Cord Injury

Overview

Journal Front Neurol

Specialty Neurology

Date 2022 Jun 27

PMID 35756929

Authors

Fei Li

Haifan Wang

Hao Chen

Jianing Guo

Xiaoqian Dang

Yi Ru

Haoyu Wang

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is a non-necrotic form of regulated cell death (RCD) that is primarily characterized by iron-dependent membrane lipid peroxidation and is regulated by cysteine transport, glutathione synthesis, and glutathione peroxidase 4 function as well as other proteins including ferroptosis suppressor protein 1. It has been found that ferroptosis played an important role in many diseases, such as neurodegenerative diseases and ischemia-reperfusion injury. Spinal cord injury (SCI), especially traumatic SCI, is an urgent problem worldwide due to its high morbidity and mortality, as well as the destruction of functions of the human body. Various RCDs, including ferroptosis, are found in SCI. Different from necrosis, since RCD is a form of cell death regulated by various molecular mechanisms in cells, the study of the role played by RCD in SCI will contribute to a deeper understanding of the pathophysiological process, as well as the treatment and functional recovery. The present review mainly introduces the main mechanism of ferroptosis and its role in SCI, so as to provide a new idea for further exploration.

Citing Articles

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References

Yant L, Ran Q, Rao L, Van Remmen H, Shibatani T, Belter J . The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic Biol Med. 2003; 34(4):496-502. DOI: 10.1016/s0891-5849(02)01360-6. View

Dai W, Wang X, Teng H, Li C, Wang B, Wang J . Celastrol inhibits microglial pyroptosis and attenuates inflammatory reaction in acute spinal cord injury rats. Int Immunopharmacol. 2018; 66:215-223. DOI: 10.1016/j.intimp.2018.11.029. View

Mutze S, Hebling U, Stremmel W, Wang J, Arnhold J, Pantopoulos K . Myeloperoxidase-derived hypochlorous acid antagonizes the oxidative stress-mediated activation of iron regulatory protein 1. J Biol Chem. 2003; 278(42):40542-9. DOI: 10.1074/jbc.M307159200. View

Kim J, Lee S, Park J, Yoo Y . TNF-alpha-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-X(L). Cell Death Differ. 2010; 17(9):1420-34. DOI: 10.1038/cdd.2010.19. View

Yoshii A, Constantine-Paton M . BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation. Nat Neurosci. 2007; 10(6):702-11. DOI: 10.1038/nn1903. View

Alim I, Caulfield J, Chen Y, Swarup V, Geschwind D, Ivanova E . Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke. Cell. 2019; 177(5):1262-1279.e25. DOI: 10.1016/j.cell.2019.03.032. View

Ponka P, Beaumont C, Richardson D . Function and regulation of transferrin and ferritin. Semin Hematol. 1998; 35(1):35-54. View

Zhang Y, Swanda R, Nie L, Liu X, Wang C, Lee H . mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation. Nat Commun. 2021; 12(1):1589. PMC: 7952727. DOI: 10.1038/s41467-021-21841-w. View

Chen D, Chu B, Yang X, Liu Z, Jin Y, Kon N . iPLA2β-mediated lipid detoxification controls p53-driven ferroptosis independent of GPX4. Nat Commun. 2021; 12(1):3644. PMC: 8206155. DOI: 10.1038/s41467-021-23902-6. View

10.

Mi Y, Gao X, Xu H, Cui Y, Zhang Y, Gou X . The Emerging Roles of Ferroptosis in Huntington's Disease. Neuromolecular Med. 2019; 21(2):110-119. DOI: 10.1007/s12017-018-8518-6. View

11.

Hardwick J, Soane L . Multiple functions of BCL-2 family proteins. Cold Spring Harb Perspect Biol. 2013; 5(2). PMC: 3552500. DOI: 10.1101/cshperspect.a008722. View

12.

Linkermann A, Skouta R, Himmerkus N, Mulay S, Dewitz C, De Zen F . Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci U S A. 2014; 111(47):16836-41. PMC: 4250130. DOI: 10.1073/pnas.1415518111. View

13.

Petrat F, de Groot H, Sustmann R, Rauen U . The chelatable iron pool in living cells: a methodically defined quantity. Biol Chem. 2002; 383(3-4):489-502. DOI: 10.1515/BC.2002.051. View

14.

Wang J, Chen G, Pantopoulos K . Nitric oxide inhibits the degradation of IRP2. Mol Cell Biol. 2005; 25(4):1347-53. PMC: 548015. DOI: 10.1128/MCB.25.4.1347-1353.2005. View

15.

Ray P, Huang B, Tsuji Y . Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24(5):981-90. PMC: 3454471. DOI: 10.1016/j.cellsig.2012.01.008. View

16.

Yeh K, Yeh M, Mims L, Glass J . Iron feeding induces ferroportin 1 and hephaestin migration and interaction in rat duodenal epithelium. Am J Physiol Gastrointest Liver Physiol. 2008; 296(1):G55-65. PMC: 3833992. DOI: 10.1152/ajpgi.90298.2008. View

17.

Chen Y, Li L, Lan J, Cui Y, Rao X, Zhao J . CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma. Mol Cancer. 2022; 21(1):11. PMC: 8725338. DOI: 10.1186/s12943-021-01466-9. View

18.

Zhu J, Berisa M, Schworer S, Qin W, Cross J, Thompson C . Transsulfuration Activity Can Support Cell Growth upon Extracellular Cysteine Limitation. Cell Metab. 2019; 30(5):865-876.e5. PMC: 6961654. DOI: 10.1016/j.cmet.2019.09.009. View

19.

Galluzzi L, Bravo-San Pedro J, Vitale I, Aaronson S, Abrams J, Adam D . Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ. 2014; 22(1):58-73. PMC: 4262782. DOI: 10.1038/cdd.2014.137. View

20.

Zhang Y, Sun C, Zhao C, Hao J, Zhang Y, Fan B . Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury. Brain Res. 2018; 1706:48-57. DOI: 10.1016/j.brainres.2018.10.023. View