Broadening Horizons: the Multifaceted Functions of Ferroptosis in Kidney Diseases

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2023 Aug 11

PMID 37564215

Authors

Qi Feng

Yang Yang

Kaidi Ren

Yingjin Qiao

Zhi Sun

Shaokang Pan

Fengxun Liu

Yong Liu

Jinling Huo

Dongwei Liu

Zhangsuo Liu

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is an iron-dependent programmed cell death pattern that is characterized by iron overload, reactive oxygen species (ROS) accumulation and lipid peroxidation. Growing viewpoints support that the imbalance of iron homeostasis and the disturbance of lipid metabolism contribute to tissue or organ injury in various kidney diseases by triggering ferroptosis. At present, the key regulators and complicated network mechanisms associated with ferroptosis have been deeply studied; however, its role in the initiation and progression of kidney diseases has not been fully revealed. Herein, we aim to discuss the features, key regulators and complicated network mechanisms associated with ferroptosis, explore the emerging roles of organelles in ferroptosis, gather its pharmacological progress, and systematically summarize the most recent discoveries about the crosstalk between ferroptosis and kidney diseases, including renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), autosomal dominant polycystic kidney disease (ADPKD), renal fibrosis, lupus nephritis (LN) and IgA nephropathy. We further conclude the potential therapeutic strategies by targeting ferroptosis for the prevention and treatment of kidney diseases and hope that this work will provide insight for the further study of ferroptosis in the pathogenesis of kidney-related diseases.

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References

Bayir H, Dixon S, Tyurina Y, Kellum J, Kagan V . Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney. Nat Rev Nephrol. 2023; 19(5):315-336. DOI: 10.1038/s41581-023-00689-x. View

Guo N . Identification of as a biomarker and contributor of ferroptosis in clear cell renal cell carcinoma. Transl Cancer Res. 2022; 11(8):2688-2699. PMC: 9459583. DOI: 10.21037/tcr-21-2157. View

Ballabio A, Bonifacino J . Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 2019; 21(2):101-118. DOI: 10.1038/s41580-019-0185-4. View

Tian Z, Li Z, Chu L, Liu Y, He J, Xin Y . Iron metabolism and chronic inflammation in IgA nephropathy. Ren Fail. 2023; 45(1):2195012. PMC: 10075521. DOI: 10.1080/0886022X.2023.2195012. View

Kim S, Kang S, Joo J, Han S, Shin H, Nam B . Characterization of ferroptosis in kidney tubular cell death under diabetic conditions. Cell Death Dis. 2021; 12(2):160. PMC: 7870666. DOI: 10.1038/s41419-021-03452-x. View

Santana-Codina N, Gikandi A, Mancias J . The Role of NCOA4-Mediated Ferritinophagy in Ferroptosis. Adv Exp Med Biol. 2021; 1301:41-57. DOI: 10.1007/978-3-030-62026-4_4. View

Schreiber R, Buchholz B, Kraus A, Schley G, Scholz J, Ousingsawat J . Lipid Peroxidation Drives Renal Cyst Growth through Activation of TMEM16A. J Am Soc Nephrol. 2019; 30(2):228-242. PMC: 6362630. DOI: 10.1681/ASN.2018010039. View

Ursini F, Maiorino M . Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic Biol Med. 2020; 152:175-185. DOI: 10.1016/j.freeradbiomed.2020.02.027. View

Zhao C, Yu D, He Z, Bao L, Feng L, Chen L . Endoplasmic reticulum stress-mediated autophagy activation is involved in cadmium-induced ferroptosis of renal tubular epithelial cells. Free Radic Biol Med. 2021; 175:236-248. DOI: 10.1016/j.freeradbiomed.2021.09.008. View

10.

Couto N, Wood J, Barber J . The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med. 2016; 95:27-42. DOI: 10.1016/j.freeradbiomed.2016.02.028. View

11.

Wang Y, Chang D, Zhao M, Chen M . Dapagliflozin Alleviates Diabetic Kidney Disease Hypoxia Inducible Factor 1α/Heme Oxygenase 1-Mediated Ferroptosis. Antioxid Redox Signal. 2023; 40(7-9):492-509. DOI: 10.1089/ars.2022.0169. View

12.

Li Q, Meng X, Hua Q . Circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/SLC7A11 by miR-770-5p. Acta Diabetol. 2022; 60(1):29-42. DOI: 10.1007/s00592-022-01961-5. View

13.

Yu R, Zhou Y, Shi S, Wang X, Huang S, Ren Y . Icariside II induces ferroptosis in renal cell carcinoma cells by regulating the miR-324-3p/GPX4 axis. Phytomedicine. 2022; 102:154182. DOI: 10.1016/j.phymed.2022.154182. View

14.

Anandhan A, Dodson M, Shakya A, Chen J, Liu P, Wei Y . NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Sci Adv. 2023; 9(5):eade9585. PMC: 9891695. DOI: 10.1126/sciadv.ade9585. View

15.

Krainz T, Gaschler M, Lim C, Sacher J, Stockwell B, Wipf P . A Mitochondrial-Targeted Nitroxide Is a Potent Inhibitor of Ferroptosis. ACS Cent Sci. 2016; 2(9):653-659. PMC: 5043442. DOI: 10.1021/acscentsci.6b00199. View

16.

Xiong D, Hu W, Han X, Cai Y . Rhein Inhibited Ferroptosis and EMT to Attenuate Diabetic Nephropathy by Regulating the Rac1/NOX1/β-Catenin Axis. Front Biosci (Landmark Ed). 2023; 28(5):100. DOI: 10.31083/j.fbl2805100. View

17.

Yang L, Liu Y, Zhou S, Feng Q, Lu Y, Liu D . Novel Insight into Ferroptosis in Kidney Diseases. Am J Nephrol. 2023; 54(5-6):184-199. DOI: 10.1159/000530882. View

18.

Kerins M, Milligan J, Wohlschlegel J, Ooi A . Fumarate hydratase inactivation in hereditary leiomyomatosis and renal cell cancer is synthetic lethal with ferroptosis induction. Cancer Sci. 2018; 109(9):2757-2766. PMC: 6125459. DOI: 10.1111/cas.13701. View

19.

Mou Y, Wu J, Zhang Y, Abdihamid O, Duan C, Li B . Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma. BMC Cancer. 2021; 21(1):18. PMC: 7786469. DOI: 10.1186/s12885-020-07726-z. View

20.

Hu J, Gu W, Ma N, Fan X, Ci X . Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signalling pathway. Br J Pharmacol. 2022; 179(15):3991-4009. DOI: 10.1111/bph.15834. View