Ferroptosis in Organ Ischemia-reperfusion Injuries: Recent Advancements and Strategies

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2024 Mar 31

PMID 38556592

Authors

Xiaoyu Luan

Peng Chen

Longyu Miao

Xinying Yuan

Chaoqun Yu

Guohu Di

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is a newly discovered type of regulated cell death participated in multiple diseases. Different from other classical cell death programs such as necrosis and apoptosis, ferroptosis involving iron-catalyzed lipid peroxidation is characterized by Fe accumulation and mitochondria alterations. The phenomenon of oxidative stress following organ ischemia-reperfusion (I/R) has recently garnered attention for its connection to the onset of ferroptosis and subsequent reperfusion injuries. This article provides a comprehensive overview underlying the mechanisms of ferroptosis, with a further focus on the latest research progress regarding interference with ferroptotic pathways in organ I/R injuries, such as intestine, lung, heart, kidney, liver, and brain. Understanding the links between ferroptosis and I/R injury may inform potential therapeutic strategies and targeted agents.

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References

Dixon S, Lemberg K, Lamprecht M, Skouta R, Zaitsev E, Gleason C . Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012; 149(5):1060-72. PMC: 3367386. DOI: 10.1016/j.cell.2012.03.042. View

Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X . Ferroptosis: process and function. Cell Death Differ. 2016; 23(3):369-79. PMC: 5072448. DOI: 10.1038/cdd.2015.158. View

Wang H, Liu C, Zhao Y, Gao G . Mitochondria regulation in ferroptosis. Eur J Cell Biol. 2019; 99(1):151058. DOI: 10.1016/j.ejcb.2019.151058. View

Li J, Cao F, Yin H, Huang Z, Lin Z, Mao N . Ferroptosis: past, present and future. Cell Death Dis. 2020; 11(2):88. PMC: 6997353. DOI: 10.1038/s41419-020-2298-2. View

Lei P, Bai T, Sun Y . Mechanisms of Ferroptosis and Relations With Regulated Cell Death: A Review. Front Physiol. 2019; 10:139. PMC: 6399426. DOI: 10.3389/fphys.2019.00139. View

Chen X, Li J, Kang R, Klionsky D, Tang D . Ferroptosis: machinery and regulation. Autophagy. 2020; 17(9):2054-2081. PMC: 8496712. DOI: 10.1080/15548627.2020.1810918. View

Lou S, Hou M, Chang H, Lee H, Chiu C, Yeh S . Breast Cancer Surgery 10-Year Survival Prediction by Machine Learning: A Large Prospective Cohort Study. Biology (Basel). 2022; 11(1). PMC: 8773427. DOI: 10.3390/biology11010047. View

Eltzschig H, Eckle T . Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011; 17(11):1391-401. PMC: 3886192. DOI: 10.1038/nm.2507. View

Won S, Fong R, Butler N, Sanchez J, Zhang Y, Wong C . Neuronal Oxidative Stress Promotes α-Synuclein Aggregation In Vivo. Antioxidants (Basel). 2022; 11(12). PMC: 9774295. DOI: 10.3390/antiox11122466. View

10.

Xie M, Cheng B, Yu S, He Y, Cao Y, Zhou T . Cuproptosis-Related MiR-21-5p/FDX1 Axis in Clear Cell Renal Cell Carcinoma and Its Potential Impact on Tumor Microenvironment. Cells. 2023; 12(1). PMC: 9818076. DOI: 10.3390/cells12010173. View

11.

Chen D, Guo Y, Li X, Zhang G, Li P . Small molecules as modulators of regulated cell death against ischemia/reperfusion injury. Med Res Rev. 2022; 42(6):2067-2101. DOI: 10.1002/med.21917. View

12.

Milto I, Suhodolo I, Prokopieva V, Klimenteva T . Molecular and Cellular Bases of Iron Metabolism in Humans. Biochemistry (Mosc). 2016; 81(6):549-64. DOI: 10.1134/S0006297916060018. View

13.

Stoyanovsky D, Tyurina Y, Shrivastava I, Bahar I, Tyurin V, Protchenko O . Iron catalysis of lipid peroxidation in ferroptosis: Regulated enzymatic or random free radical reaction?. Free Radic Biol Med. 2018; 133:153-161. PMC: 6555767. DOI: 10.1016/j.freeradbiomed.2018.09.008. View

14.

Frazer D, Anderson G . The regulation of iron transport. Biofactors. 2013; 40(2):206-14. DOI: 10.1002/biof.1148. View

15.

Lane D, Merlot A, Huang M, Bae D, Jansson P, Sahni S . Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease. Biochim Biophys Acta. 2015; 1853(5):1130-44. DOI: 10.1016/j.bbamcr.2015.01.021. View

16.

Bogdan A, Miyazawa M, Hashimoto K, Tsuji Y . Regulators of Iron Homeostasis: New Players in Metabolism, Cell Death, and Disease. Trends Biochem Sci. 2016; 41(3):274-286. PMC: 4783254. DOI: 10.1016/j.tibs.2015.11.012. View

17.

Kertmen A, Petrenko I, Schimpf C, Rafaja D, Petrova O, Sivkov V . Calcite Nanotuned Chitinous Skeletons of Giant Marine Demosponge. Int J Mol Sci. 2021; 22(22). PMC: 8621073. DOI: 10.3390/ijms222212588. View

18.

Lewerenz J, Hewett S, Huang Y, Lambros M, Gout P, Kalivas P . The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal. 2012; 18(5):522-55. PMC: 3545354. DOI: 10.1089/ars.2011.4391. View

19.

Conrad M, Sato H . The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond. Amino Acids. 2011; 42(1):231-46. DOI: 10.1007/s00726-011-0867-5. View

20.

Lu S . Glutathione synthesis. Biochim Biophys Acta. 2012; 1830(5):3143-53. PMC: 3549305. DOI: 10.1016/j.bbagen.2012.09.008. View