Ferritinophagy Induced Ferroptosis in the Management of Cancer

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2023 Sep 15

PMID 37713105

Authors

Yi-Chen Liu

Yi-Ting Gong

Qing-Yan Sun

Bei Wang

Yue Yan

Yi-Xu Chen

Li-Jun Zhang

Wei-Dong Zhang

Xin Luan

Affiliations

Soon will be listed here.

Abstract

Background: Ferroptosis, a newly form of regulated cell death (RCD), is characterized by iron dyshomeostasis and unrestricted lipid peroxidation. Emerging evidence depicts a pivotal role for ferroptosis in driving some pathological processes, especially in cancer. Triggering ferroptosis can suppress tumor growth and induce an anti-tumor immune response, denoting the therapeutic promises for targeting ferroptosis in the management of cancer. As an autophagic phenomenon, ferritinophagy is critical to induce ferroptosis by degradation of ferritin to release intracellular free iron. Recently, a great deal of effort has gone into designing and developing anti-cancer strategies based on targeting ferritinophagy to induce ferroptosis.

Conclusion: This review delineates the regulatory mechanism of ferritinophagy firstly and summarizes the role of ferritinophagy-induced ferroptosis in cancer. Moreover, the strategies targeting ferritinophagy to induce ferroptosis are highlighted to unveil the therapeutic value of ferritinophagy as a target to manage cancer. Finally, the future research directions on how to cope with the challenges in developing ferritinophagy promoters into clinical therapeutics are discussed.

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References

Gao M, Jiang X . To eat or not to eat-the metabolic flavor of ferroptosis. Curr Opin Cell Biol. 2017; 51:58-64. PMC: 5949249. DOI: 10.1016/j.ceb.2017.11.001. View

Galluzzi L, Vitale I, Aaronson S, Abrams J, Adam D, Agostinis P . Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018; 25(3):486-541. PMC: 5864239. DOI: 10.1038/s41418-017-0012-4. View

Koren E, Fuchs Y . Modes of Regulated Cell Death in Cancer. Cancer Discov. 2021; 11(2):245-265. DOI: 10.1158/2159-8290.CD-20-0789. View

Dixon S, Stockwell B . The role of iron and reactive oxygen species in cell death. Nat Chem Biol. 2013; 10(1):9-17. DOI: 10.1038/nchembio.1416. View

Tang D, Kroemer G . Ferroptosis. Curr Biol. 2020; 30(21):R1292-R1297. DOI: 10.1016/j.cub.2020.09.068. 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

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

Wang W, Green M, Choi J, Gijon M, Kennedy P, Johnson J . CD8 T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019; 569(7755):270-274. PMC: 6533917. DOI: 10.1038/s41586-019-1170-y. View

Chang H, Zou Z . Targeting autophagy to overcome drug resistance: further developments. J Hematol Oncol. 2020; 13(1):159. PMC: 7687716. DOI: 10.1186/s13045-020-01000-2. View

10.

Levine B, Mizushima N, Virgin H . Autophagy in immunity and inflammation. Nature. 2011; 469(7330):323-35. PMC: 3131688. DOI: 10.1038/nature09782. View

11.

Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X . Ferroptosis is an autophagic cell death process. Cell Res. 2016; 26(9):1021-32. PMC: 5034113. DOI: 10.1038/cr.2016.95. View

12.

Ajoolabady A, Aslkhodapasandhokmabad H, Libby P, Tuomilehto J, Lip G, Penninger J . Ferritinophagy and ferroptosis in the management of metabolic diseases. Trends Endocrinol Metab. 2021; 32(7):444-462. DOI: 10.1016/j.tem.2021.04.010. View

13.

Latunde-Dada G . Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy. Biochim Biophys Acta Gen Subj. 2017; 1861(8):1893-1900. DOI: 10.1016/j.bbagen.2017.05.019. View

14.

Stockwell B, Jiang X, Gu W . Emerging Mechanisms and Disease Relevance of Ferroptosis. Trends Cell Biol. 2020; 30(6):478-490. PMC: 7230071. DOI: 10.1016/j.tcb.2020.02.009. View

15.

Tang D, Chen X, Kang R, Kroemer G . Ferroptosis: molecular mechanisms and health implications. Cell Res. 2020; 31(2):107-125. PMC: 8026611. DOI: 10.1038/s41422-020-00441-1. View

16.

Bai Y, Meng L, Han L, Jia Y, Zhao Y, Gao H . Lipid storage and lipophagy regulates ferroptosis. Biochem Biophys Res Commun. 2018; 508(4):997-1003. DOI: 10.1016/j.bbrc.2018.12.039. View

17.

Yang M, Chen P, Liu J, Zhu S, Kroemer G, Klionsky D . Clockophagy is a novel selective autophagy process favoring ferroptosis. Sci Adv. 2019; 5(7):eaaw2238. PMC: 6656546. DOI: 10.1126/sciadv.aaw2238. View

18.

Wu Z, Geng Y, Lu X, Shi Y, Wu G, Zhang M . Chaperone-mediated autophagy is involved in the execution of ferroptosis. Proc Natl Acad Sci U S A. 2019; 116(8):2996-3005. PMC: 6386716. DOI: 10.1073/pnas.1819728116. View

19.

Gao M, Yi J, Zhu J, Minikes A, Monian P, Thompson C . Role of Mitochondria in Ferroptosis. Mol Cell. 2018; 73(2):354-363.e3. PMC: 6338496. DOI: 10.1016/j.molcel.2018.10.042. View

20.

Muckenthaler M, Rivella S, Hentze M, Galy B . A Red Carpet for Iron Metabolism. Cell. 2017; 168(3):344-361. PMC: 5706455. DOI: 10.1016/j.cell.2016.12.034. View