The Latest View on the Mechanism of Ferroptosis and Its Research Progress in Spinal Cord Injury

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2020 Sep 10

PMID 32908634

Citations 37

Authors

Yixin Chen

Suixin Liu

Jianjun Li

Zhe Li

Jing Quan

Xinzhou Liu

Yinbo Tang

Bin Liu

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is a recently identified nonapoptotic form of cell death whose major markers are iron dependence and accumulation of lipid reactive oxygen species, accompanied by morphological changes such as shrunken mitochondria and increased membrane density. It appears to contribute to the death of tumors, ischemia-reperfusion, acute renal failure, and nervous system diseases, among others. The generative mechanism of ferroptosis includes iron overloading, lipid peroxidation, and downstream execution, while the regulatory mechanism involves the glutathione/glutathione peroxidase 4 pathway, as well as the mevalonate pathway and the transsulfuration pathway. In-depth research has continuously developed and enriched knowledge on the mechanism by which ferroptosis occurs. In recent years, reports of the noninterchangeable role played by selenium in glutathione peroxidase 4 and its function in suppressing ferroptosis and the discovery of ferroptosis suppressor protein 1, identified as a ferroptosis resistance factor parallel to the glutathione peroxidase 4 pathway, have expanded and deepened our understanding of the mechanism by which ferroptosis works. Ferroptosis has been reported in spinal cord injury animal model experiments, and the inhibition of ferroptosis could promote the recovery of neurological function. Here, we review the latest studies on mechanism by which ferroptosis occurs, focusing on the ferroptosis execution and the contents related to selenium and ferroptosis suppressor protein 1. In addition, we summarize the current research status of ferroptosis in spinal cord injury. The aim of this review is to better understand the mechanisms by which ferroptosis occurs and its role in the pathophysiological process of spinal cord injury, so as to provide a new idea and frame of reference for further exploration.

Citing Articles

Ferroptosis, pathogenesis and therapy in AS co-depression disease.

Zhao Y, Ren P, Luo Q, Li X, Cheng X, Wen Y Front Pharmacol. 2025; 16:1516601.

PMID: 40066336 PMC: 11891183. DOI: 10.3389/fphar.2025.1516601.

Bioinformatics analysis of genes associated with disulfidptosis in spinal cord injury.

Wang S, Liu X, Tian J, Liu S, Ke L, Zhang S PLoS One. 2025; 20(2):e0318016.

PMID: 39951434 PMC: 11828381. DOI: 10.1371/journal.pone.0318016.

The Interplay Between Endoplasmic Reticulum Stress and Ferroptosis in Neurological Diseases.

Zhai T, Wang B, Shi C, Zhang C, Shen J, Feng X Neurochem Res. 2025; 50(2):99.

PMID: 39928173 DOI: 10.1007/s11064-025-04348-4.

Integrated bioinformatics analysis identified cuproptosis-related hub gene Mpeg1 as potential biomarker in spinal cord injury.

Mao D, Chen Q, Tong S, Xu Z, Yu G, Chang C Sci Rep. 2025; 15(1):1993.

PMID: 39814871 PMC: 11736097. DOI: 10.1038/s41598-025-86170-0.

LncRNA OIP5-AS1 regulates ferroptosis and mitochondrial dysfunction-mediated apoptosis in spinal cord injury by targeting the miR-128-3p/Nrf2 axis.

Jiang Z, Zhang W, Zhang J Heliyon. 2024; 10(18):e37704.

PMID: 39309798 PMC: 11416499. DOI: 10.1016/j.heliyon.2024.e37704.

References

Yang W, Stockwell B . Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008; 15(3):234-45. PMC: 2683762. DOI: 10.1016/j.chembiol.2008.02.010. View

Overholtzer M, Mailleux A, Mouneimne G, Normand G, Schnitt S, King R . A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell. 2007; 131(5):966-79. DOI: 10.1016/j.cell.2007.10.040. 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

Yang W, Shimada K, Delva D, Patel M, Ode E, Skouta R . Identification of Simple Compounds with Microtubule-Binding Activity That Inhibit Cancer Cell Growth with High Potency. ACS Med Chem Lett. 2012; 3(1):35-38. PMC: 3256933. DOI: 10.1021/ml200195s. View

Mas E, Mori T . Coenzyme Q(10) and statin myalgia: what is the evidence?. Curr Atheroscler Rep. 2010; 12(6):407-13. DOI: 10.1007/s11883-010-0134-3. View

Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G, Buday K . Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis. Cell. 2018; 172(3):409-422.e21. DOI: 10.1016/j.cell.2017.11.048. View

Holstein S, Hohl R . Isoprenoids: remarkable diversity of form and function. Lipids. 2004; 39(4):293-309. DOI: 10.1007/s11745-004-1233-3. View

Ding D, Przybylowski C, Starke R, Sterling Street R, Tyree A, Crowley R . A minimally invasive anterior skull base approach for evacuation of a basal ganglia hemorrhage. J Clin Neurosci. 2015; 22(11):1816-9. DOI: 10.1016/j.jocn.2015.03.052. View

Conrad M, Friedmann Angeli J, Vandenabeele P, Stockwell B . Regulated necrosis: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 2016; 15(5):348-66. PMC: 6531857. DOI: 10.1038/nrd.2015.6. View

10.

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

11.

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

12.

Emery E, Aldana P, Bunge M, PUCKETT W, Srinivasan A, Keane R . Apoptosis after traumatic human spinal cord injury. J Neurosurg. 1998; 89(6):911-20. DOI: 10.3171/jns.1998.89.6.0911. View

13.

Schwaller B, Tetko I, Tandon P, Silveira D, Vreugdenhil M, Henzi T . Parvalbumin deficiency affects network properties resulting in increased susceptibility to epileptic seizures. Mol Cell Neurosci. 2004; 25(4):650-63. DOI: 10.1016/j.mcn.2003.12.006. View

14.

Fink S, Cookson B . Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun. 2005; 73(4):1907-16. PMC: 1087413. DOI: 10.1128/IAI.73.4.1907-1916.2005. View

15.

Doll S, Proneth B, Tyurina Y, Panzilius E, Kobayashi S, Ingold I . ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2016; 13(1):91-98. PMC: 5610546. DOI: 10.1038/nchembio.2239. View

16.

Hadian K . Ferroptosis Suppressor Protein 1 (FSP1) and Coenzyme Q Cooperatively Suppress Ferroptosis. Biochemistry. 2020; 59(5):637-638. DOI: 10.1021/acs.biochem.0c00030. View

17.

Doll S, Porto Freitas F, Shah R, Aldrovandi M, Costa Da Silva M, Ingold I . FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019; 575(7784):693-698. DOI: 10.1038/s41586-019-1707-0. View

18.

Magtanong L, Ko P, Dixon S . Emerging roles for lipids in non-apoptotic cell death. Cell Death Differ. 2016; 23(7):1099-109. PMC: 5399169. DOI: 10.1038/cdd.2016.25. View

19.

Tang D, Kang R, Vanden Berghe T, Vandenabeele P, Kroemer G . The molecular machinery of regulated cell death. Cell Res. 2019; 29(5):347-364. PMC: 6796845. DOI: 10.1038/s41422-019-0164-5. View

20.

Hayano M, Yang W, Corn C, Pagano N, Stockwell B . Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ. 2015; 23(2):270-8. PMC: 4716307. DOI: 10.1038/cdd.2015.93. View