Full Text:   <417>

Summary:  <97>

CLC number: 

On-line Access: 2024-01-02

Received: 2023-02-13

Revision Accepted: 2023-05-21

Crosschecked: 2024-01-02

Cited: 0

Clicked: 589

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.1 P.1-22

http://doi.org/10.1631/jzus.B2300097


Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases


Author(s):  Yi LUAN, Yang YANG, Ying LUAN, Hui LIU, Han XING, Jinyan PEI, Hengdao LIU, Bo QIN, Kaidi REN

Affiliation(s):  Clinical Systems Biology Research Laboratories, Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; more

Corresponding email(s):   renkd006@163.com, boqin@mail.ustc.edu.cn, fccliuhd@zzu.edu.cn

Key Words:  Cardiovascular disease, Iron, Ferroptosis, Ferritinophagy, Therapeutic target


Share this article to: More |Next Article >>>

Yi LUAN, Yang YANG, Ying LUAN, Hui LIU, Han XING, Jinyan PEI, Hengdao LIU, Bo QIN, Kaidi REN. Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases[J]. Journal of Zhejiang University Science B, 2024, 25(1): 1-22.

@article{title="Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases",
author="Yi LUAN, Yang YANG, Ying LUAN, Hui LIU, Han XING, Jinyan PEI, Hengdao LIU, Bo QIN, Kaidi REN",
journal="Journal of Zhejiang University Science B",
volume="25",
number="1",
pages="1-22",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300097"
}

%0 Journal Article
%T Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases
%A Yi LUAN
%A Yang YANG
%A Ying LUAN
%A Hui LIU
%A Han XING
%A Jinyan PEI
%A Hengdao LIU
%A Bo QIN
%A Kaidi REN
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 1
%P 1-22
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300097

TY - JOUR
T1 - Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases
A1 - Yi LUAN
A1 - Yang YANG
A1 - Ying LUAN
A1 - Hui LIU
A1 - Han XING
A1 - Jinyan PEI
A1 - Hengdao LIU
A1 - Bo QIN
A1 - Kaidi REN
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 1
SP - 1
EP - 22
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300097


Abstract: 
cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

靶向铁死亡和铁自噬:心血管疾病的新靶点?

栾一1,杨阳1,栾莹2,刘慧3,邢晗7,8,9,裴金燕4,刘恒道5,秦波6,任凯迪7,8,9
1郑州大学第一附属医院,临床系统生物学研究中心,中国郑州市,450052
2北京大学物理科学学院,中国北京市,100871
3新乡医科大学医学检验学院,中国新乡市,453003
4河南省省直第三人民医院,质量管理办公室,中国郑州市,450052
5郑州大学第一附属医院心内科,中国郑州市,450052
6郑州大学第一附属医院转化医学中心,中国郑州市,450052
7郑州大学第一附属医院药学部,中国郑州市,450052
8郑州大学河南省精准用药重点实验室,中国郑州市,450052
9郑州大学河南省精准用药转化与应用工程实验中心,中国郑州市,450052
摘要:心血管疾病(CVDs)在全球范围内是死亡的主要驱动因素。铁是一种必需的微量元素,在多种生物过程中很重要。几十年来,铁对心血管疾病的作用引起了广泛的讨论。由铁介导的细胞死亡方式,即铁死亡,在心肌细胞损伤和心血管疾病中发挥着重要的作用,因此受到广泛关注。此外,铁自噬是诱导铁死亡的上游机制,与心血管疾病密切相关。本文就铁死亡和铁自噬的过程、机制、铁自噬的调控途径和分子靶点进行综述,并总结其对心血管疾病的作用。此外,我们讨论了针对铁自噬诱导的铁死亡调节剂治疗心血管疾病的可能性。总之,本综述将为心血管疾病的病理学机制提供新的见解,并提供一系列潜在治疗靶点。

关键词:心血管疾病;铁;铁死亡;铁自噬;治疗靶点

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AjoolabadyA, AslkhodapasandhokmabadH, LibbyP, et al., 2021. Ferritinophagy and ferroptosis in the management of metabolic diseases. Trends Endocrinol Metab, 32(7):444-462.

[2]AladağN, AsoğluR, OzdemirM, et al., 2021. Oxidants and antioxidants in myocardial infarction (MI): investigation of ischemia modified albumin, malondialdehyde, superoxide dismutase and catalase in individuals diagnosed with ST elevated myocardial infarction (STEMI) and non-STEMI (NSTEMI). J Med Biochem, 40(3):286-294.

[3]AllwoodMA, KinobeRT, BallantyneL, et al., 2014. Heme oxygenase-1 overexpression exacerbates heart failure with aging and pressure overload but is protective against isoproterenol-induced cardiomyopathy in mice. Cardiovasc Pathol, 23(4):231-237.

[4]BabaY, HigaJK, ShimadaBK, et al., 2018. Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am J Physiol Heart Circ Physiol, 314(3):H659-H668.

[5]BaiT, LiMX, LiuYF, et al., 2020. Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell. Free Radic Biol Med, 160:92-102.

[6]BaiYT, ChangR, WangH, et al., 2018. ENPP2 protects cardiomyocytes from erastin-induced ferroptosis. Biochem Biophys Res Commun, 499(1):44-51.

[7]BanjacA, PerisicT, SatoH, et al., 2008. The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death. Oncogene, 27(11):1618-1628.

[8]BauckmanKA, MysorekarIU, 2016. Ferritinophagy drives uropathogenic Escherichia coli persistence in bladder epithelial cells. Autophagy, 12(5):850-863.

[9]BeaumontJL, BeaumontV, LenegreJ, 1958. Research on lipid metabolism in human atherosclerosis. II. Multiple aspects of blood lipids in angina pectoris. Rev Fr Etud Clin Biol, 3(8):852-868.

[10]BersukerK, HendricksJM, LiZP, et al., 2019. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature, 575(7784):688-692.

[11]ChenXQ, XuSD, ZhaoCX, et al., 2019. Role of TLR4/NADPH oxidase 4 pathway in promoting cell death through autophagy and ferroptosis during heart failure. Biochem Biophys Res Commun, 516(1):37-43.

[12]ChuaACG, GrahamRM, TrinderD, et al., 2007. The regulation of cellular iron metabolism. Crit Rev Clin Lab Sci, 44(5-6):413-459.

[13]ClarkeSL, VasanthakumarA, AndersonSA, et al., 2006. Iron-responsive degradation of iron-regulatory protein 1 does not require the Fe–S cluster. EMBO J, 25(3):544-553.

[14]CorradiM, MuttiA, 2011. Metal ions affecting the pulmonary and cardiovascular systems. Met Ions Life Sci, 8:81-105.

[15]del ReyMQ, ManciasJD, 2019. NCOA4-mediated ferritinophagy: a potential link to neurodegeneration. Front Neurosci, 13:238.

[16]DingM, FengRT, WangSY, et al., 2006. Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J Biol Chem, 281(25):17359-17368.

[17]DoddS, DeanO, CopolovDL, et al., 2008. N-Acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther, 8(12):1955-1962.

[18]DollS, FreitasFP, ShahR, et al., 2019. FSP1 is a glutathione-independent ferroptosis suppressor. Nature, 575(7784):693-698.

[19]DrysdaleJ, ArosioP, InvernizziR, et al., 2002. Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol Dis, 29(3):376-383.

[20]ErberLN, LuoA, GongY, et al., 2021. Iron deficiency reprograms phosphorylation signaling and reduces O-GlcNAc pathways in neuronal cells. Nutrients, 13(1):179.

[21]FangXX, WangH, HanD, et al., 2019. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci USA, 116(7):2672-2680.

[22]FangXX, CaiZX, WangH, et al., 2020. Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ Res, 127(4):486-501.

[23]FangXX, ArdehaliH, MinJX, et al., 2023. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease. Nat Rev Cardiol, 20:7-23.

[24]FengYS, MadungweNB, AliaganADI, et al., 2019. Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels. Biochem Biophys Res Commun, 520(3):606-611.

[25]FisherSA, BrunskillSJ, DoreeC, et al., 2013a. Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. Cochrane Database Syst Rev, (8):CD004450.

[26]FisherSA, BrunskillSJ, DoreeC, et al., 2013b. Oral deferiprone for iron chelation in people with thalassaemia. Cochrane Database Syst Rev, (8):CD004839.

[27]FlemingMD, 2008. The regulation of hepcidin and its effects on systemic and cellular iron metabolism. Hematology Am Soc Hematol Educ Program, 2008(1):151-158.

[28]FoxNG, DasD, ChakrabartiM, et al., 2015. Frataxin accelerates [2Fe-2S] cluster formation on the human Fe‍–‍S assembly complex. Biochemistry, 54(25):3880-3889.

[29]FuhrmannDC, MondorfA, BeifußJ, et al., 2020. Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis. Redox Biol, 36:101670.

[30]FujimakiM, FuruyaN, SaikiS, et al., 2019. Iron supply via NCOA4-mediated ferritin degradation maintains mitochondrial functions. Mol Cell Biol, 39(14):e00010-19.

[31]GanBY, 2021. Mitochondrial regulation of ferroptosis. J Cell Biol, 220(9):e202105043.

[32]GanBY, 2022. ACSL4, PUFA, and ferroptosis: new arsenal in anti-tumor immunity. Signal Transduct Target Ther, 7:128.

[33]GaoGF, ChangYZ, 2014. Mitochondrial ferritin in the regulation of brain iron homeostasis and neurodegenerative diseases. Front Pharmacol, 5:19.

[34]GaoJY, ZhouQL, WuD, et al., 2021. Mitochondrial iron metabolism and its role in diseases. Clin Chim Acta, 513:6-12.

[35]GaoZ, GaoQ, LvXD, 2020. MicroRNA-668-3p protects against oxygen-glucose deprivation in a rat H9c2 cardiomyocyte model of ischemia-reperfusion injury by targeting the stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling pathway. Med Sci Monit, 26:e919601.

[36]GianazzaE, BrioschiM, FernandezAM, et al., 2021. Lipid peroxidation in atherosclerotic cardiovascular diseases. Antioxid Redox Signal, 34(1):49-98.

[37]GrahamL, OrensteinJM, 2007. Processing tissue and cells for transmission electron microscopy in diagnostic pathology and research. Nat Protoc, 2(10):2439-2450.

[38]GryzikM, AspertiM, DenardoA, et al., 2021. NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells. Biochim Biophys Acta Mol Cell Res, 1868(2):118913.

[39]GuCZ, ChangWJ, WuJL, et al., 2022. NCOA4: an immunomodulation-related prognostic biomarker in colon adenocarcinoma and pan-cancer. J Oncol, 2022:5242437.

[40]GuoJD, ZhaoX, LiY, et al., 2018. Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease (Review). Int J Mol Med, 41(4):1817-1825.

[41]GuoZM, RanQT, RobertsLJ II, et al., 2008. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Free Radic Biol Med, 44(3):343-352.

[42]HanC, LiuYY, DaiRJ, et al., 2020. Ferroptosis and its potential role in human diseases. Front Pharmacol, 11:239.

[43]HanJW, KangC, KimY, et al., 2020. Isoproterenol-induced hypertrophy of neonatal cardiac myocytes and H9c2 cell is dependent on TRPC3-regulated Cav1.2 expression. Cell Calcium, 92:102305.

[44]HanXJ, ZhangJ, LiuJ, et al., 2023. Targeting ferroptosis: a novel insight against myocardial infarction and ischemia-reperfusion injuries. Apoptosis, 28:108-123.

[45]HenningerC, FritzG, 2018. Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers. Cell Death Dis, 8:e2564.

[46]HinmanA, HolstCR, LathamJC, et al., 2018. Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. PLoS ONE, 13(8):e0201369.

[47]HollenbergSM, SingerM, 2021. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol, 18(6):424-434.

[48]HouW, XieYC, SongXX, et al., 2016. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy, 12(8):1425-1428.

[49]HuangTF, SunYJ, LiYL, et al., 2018. Growth inhibition of a novel iron chelator, DpdtC, against hepatoma carcinoma cell lines partly attributed to ferritinophagy-mediated lysosomal ROS generation. Oxid Med Cell Longev, 2018:4928703.

[50]ImaiH, MatsuokaM, KumagaiT, et al., 2017. Lipid peroxidation-dependent cell death regulated by GPx4 and ferroptosis. Curr Top Microbiol Immunol, 403:143-170.

[51]ItoJ, OmiyaS, RusuMC, et al., 2021. Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice. eLife, 10:e62174.

[52]JavadovS, 2022. Mitochondria and ferroptosis. Curr Opin Physiol, 25:100483.

[53]JiangJJ, ZhangGF, ZhengJY, et al., 2022. Targeting mitochondrial ROS-mediated ferroptosis by quercetin alleviates high-fat diet-induced hepatic lipotoxicity. Front Pharmacol, 13:876550.

[54]JiangXJ, StockwellBR, ConradM, 2021. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 22(4):266-282.

[55]JinT, HeQ, ChengC, et al., 2022. UAMC-3203 or/and deferoxamine improve post-resuscitation myocardial dysfunction through suppressing ferroptosis in a rat model of cardiac arrest. Shock, 57(3):344-350.

[56]KaneMD, SchwarzRD, St. Pierre L, et al., 1999. Inhibitors of V-type ATPases, bafilomycin A1 and concanamycin A, protect against β‍-amyloid-mediated effects on 3-‍(4,5-dimethylthiazol-2-yl)‍-2,‍5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem, 72(5):1939-1947.

[57]KangH, HanMR, XueJ, et al., 2019. Renal clearable nanochelators for iron overload therapy. Nat Commun, 10:5134.

[58]KitakataH, EndoJ, IkuraH, et al., 2022. Therapeutic targets for DOX-induced cardiomyopathy: role of apoptosis vs. ferroptosis. Int J Mol Sci, 23(3):1414.

[59]KoleiniN, ShapiroJS, GeierJ, et al., 2021. Ironing out mechanisms of iron homeostasis and disorders of iron deficiency. J Clin Invest, 131(11):e148671.

[60]KollaraA, BrownTJ, 2012. Expression and function of nuclear receptor co-activator 4: evidence of a potential role independent of co-activator activity. Cell Mol Life Sci, 69(23):3895-3909.

[61]KopinskiPK, SinghLN, ZhangSP, et al., 2021. Mitochondrial DNA variation and cancer. Nat Rev Cancer, 21(7):431-445.

[62]LaiYF, DongJ, WuY, et al., 2022. Lipid peroxides mediated ferroptosis in electromagnetic pulse-induced hippocampal neuronal damage via inhibition of GSH/GPX4 axis. Int J Mol Sci, 23(16):9277.

[63]Lakhal-LittletonS, 2019. Iron deficiency as a therapeutic target in cardiovascular disease. Pharmaceuticals, 12(3):125.

[64]LanHY, GaoY, ZhaoZY, et al., 2022. Ferroptosis: redox imbalance and hematological tumorigenesis. Front Oncol, 12:834681.

[65]LeeHL, HeeSW, HsuanCF, et al., 2021. A novel ALDH2 activator AD-9308 improves diastolic and systolic myocardial functions in streptozotocin-induced diabetic mice. Antioxidants, 10(3):450.

[66]LeeJC, ChiangKC, FengTH, et al., 2016. The iron chelator, Dp44mT, effectively inhibits human oral squamous cell carcinoma cell growth in vitro and in vivo. Int J Mol Sci, 17(9):1435.

[67]LeeJY, KimWK, BaeKH, et al., 2021. Lipid metabolism and ferroptosis. Biology, 10(3):184.

[68]LeeYS, LeeDH, ChoudryHA, et al., 2018. Ferroptosis-induced endoplasmic reticulum stress: cross-talk between ferroptosis and apoptosis. Mol Cancer Res, 16(7):‍‍1073-1076.

[69]LeiG, ZhuangL, GanBY, 2022. Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer, 22(7):381-396.

[70]LengYL, LuoX, YuJY, et al., 2022. Ferroptosis: a potential target in cardiovascular disease. Front Cell Dev Biol, 9:813668.

[71]LiC, SunGC, ChenBL, et al., 2021. Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke. Pharmacol Res, 174:105933.

[72]LiC, WuZY, XueH, et al., 2022. Ferroptosis contributes to hypoxic-ischemic brain injury in neonatal rats: role of the SIRT1/Nrf2/GPx4 signaling pathway. CNS Neurosci Ther, 28(12):2268-2280.

[73]LiFJ, LongHZ, ZhouZW, et al., 2022. System Xc-/GSH/GPX4 axis: an important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy. Front Pharmacol, 13:910292.

[74]LiN, WangW, ZhouH, et al., 2020. Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury. Free Radic Biol Med, 160:303-318.

[75]LiN, JiangWY, WangW, et al., 2021. Ferroptosis and its emerging roles in cardiovascular diseases. Pharmacol Res, 166:105466.

[76]LiQ, HanXN, LanX, et al., 2017. Inhibition of neuronal ferroptosis protects hemorrhagic brain. JCI Insight, 2(7):e90777.

[77]LiSY, WangR, WangYX, et al., 2022. Ferroptosis: a new insight for treatment of acute kidney injury. Front Pharmacol, 13:1065867.

[78]LiSZ, ZhangXY, 2021. Iron in cardiovascular disease: challenges and potentials. Front Cardiovasc Med, 8:707138.

[79]LiXQ, LozovatskyL, SukumaranA, et al., 2020. NCOA4 is regulated by HIF and mediates mobilization of murine hepatic iron stores after blood loss. Blood, 136(23):‍2691-2702.

[80]LinMM, LiuN, QinZH, et al., 2022. Mitochondrial-derived damage-associated molecular patterns amplify neuroinflammation in neurodegenerative diseases. Acta Pharmacol Sin, 43(10):2439-2447.

[81]LinPL, TangHH, WuSY, et al., 2020. Saponin formosanin C-induced ferritinophagy and ferroptosis in human hepatocellular carcinoma cells. Antioxidants, 9(8):682.

[82]LittarruGP, LangsjoenP, 2007. Coenzyme Q10 and statins: biochemical and clinical implications. Mitochondrion, 7:S168-S174.

[83]LiuB, ZhaoCX, LiHK, et al., 2018. Puerarin protects against heart failure induced by pressure overload through mitigation of ferroptosis. Biochem Biophys Res Commun, 497(1):233-240.

[84]LiuJP, CenSY, XueZA, et al., 2022. A class of disulfide compounds suppresses ferroptosis by stabilizing GPX4. ACS Chem Biol, 17(12):3389-3406.

[85]LiuM, KongXY, YaoY, et al., 2022. The critical role and molecular mechanisms of ferroptosis in antioxidant systems: a narrative review. Ann Transl Med, 10(6):368.

[86]LiuMR, ZhuWT, PeiDS, 2021. System Xc-: a key regulatory target of ferroptosis in cancer. Invest New Drugs, 39(4):1123-1131.

[87]LiuMZ, KongN, ZhangGY, et al., 2022. The critical role of ferritinophagy in human disease. Front Pharmacol, 13:933732.

[88]LiuPF, FengYT, LiHW, et al., 2020. Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis. Cell Mol Biol Lett, 25:10.

[89]LiuR, ZhiXY, ZhongQ, 2015. ATG14 controls SNARE-mediated autophagosome fusion with a lysosome. Autophagy, 11(5):847-849.

[90]LiuX, DuSW, WangSD, et al., 2022. Ferroptosis in osteosarcoma: a promising future. Front Oncol, 12:1031779.

[91]LiuXM, LiDL, PiWH, et al., 2022. LCZ696 protects against doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via AKT/SIRT3/SOD2 signaling pathway activation. Int Immunopharmacol, 113:109379.

[92]LiuY, WangW, LiYY, et al., 2015. The 5-lipoxygenase inhibitor zileuton confers neuroprotection against glutamate oxidative damage by inhibiting ferroptosis. Biol Pharm Bull, 38(8):1234-1239.

[93]LiuYC, ZengLP, YangY, et al., 2020. Acyl-CoA thioesterase 1 prevents cardiomyocytes from Doxorubicin-induced ferroptosis via shaping the lipid composition. Cell Death Dis, 11(9):756.

[94]LuLQ, WuD, LiLF, et al., 2017. Apelin/APJ system: a bifunctional target for cardiac hypertrophy. Int J Cardiol, 230:164-170.

[95]LuLQ, TianJ, LuoXJ, et al., 2021. Targeting the pathways of regulated necrosis: a potential strategy for alleviation of cardio-cerebrovascular injury. Cell Mol Life Sci, 78:63-78.

[96]LuanY, LuanY, FengQ, et al., 2021a. Emerging role of mitophagy in the heart: therapeutic potentials to modulate mitophagy in cardiac diseases. Oxid Med Cell Longev, 2021:3259963.

[97]LuanY, RenKD, LuanY, et al., 2021b. Mitochondrial dynamics: pathogenesis and therapeutic targets of vascular diseases. Front Cardiovasc Med, 8:770574.

[98]LuanY, LuanY, YuanRX, et al., 2021c. Structure and function of mitochondria-associated endoplasmic reticulum membranes (MAMs) and their role in cardiovascular diseases. Oxid Med Cell Longev, 2021:4578809.

[99]LuoY, ApaijaiN, LiaoSC, et al., 2022. Therapeutic potentials of cell death inhibitors in rats with cardiac ischaemia/reperfusion injury. J Cell Mol Med, 26(8):‍2462-2476.

[100]LvXH, JiangHH, LiBG, et al., 2014. The crucial role of Atg5 in cortical neurogenesis during early brain development. Sci Rep, 4:6010.

[101]LvYH, WuMY, WangZ, et al., 2022. Ferroptosis: from regulation of lipid peroxidation to the treatment of diseases. Cell Biol Toxicol, 39:827-851.

[102]MaTY, DuJT, ZhangYF, et al., 2022. GPX4-independent ferroptosis—a new strategy in disease’s therapy. Cell Death Discov, 8:434.

[103]MaineMD, 1979. Role of trace metals in regulation of cellular heme and hemoprotein metabolism: sensitizing effects of chronic iron treatment on acute gold toxicity. Drug Metab Rev, 9(2):237-255.

[104]ManciasJD, VaitesLP, NissimS, et al., 2015. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. Elife, 4:e10308.

[105]MaoC, LiuXG, ZhangYL, et al., 2021. DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature, 593(7860):586-590.

[106]MengZJ, LiangHP, ZhaoJL, et al., 2021. HMOX1 upregulation promotes ferroptosis in diabetic atherosclerosis. Life Sci, 284:119935.

[107]MinakakiG, MengesS, KittelA, et al., 2018. Autophagy inhibition promotes SNCA/alpha-synuclein release and transfer via extracellular vesicles with a hybrid autophagosome-exosome-like phenotype. Autophagy, 14(1):98-119.

[108]MishimaE, ItoJ, WuZJ, et al., 2022. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature, 608(7924):778-783.

[109]MoYS, DuanLN, YangYN, et al., 2021. Nanoparticles improved resveratrol brain delivery and its therapeutic efficacy against intracerebral hemorrhage. Nanoscale, 13(6):3827-3840.

[110]MohantySK, DonnellyB, TempleH, et al., 2021. High mobility group box 1 release by cholangiocytes governs biliary atresia pathogenesis and correlates with increases in afflicted infants. Hepatology, 74(2):864-878.

[111]OmiyaS, ItoJ, OtsuL, 2021. Labile iron derived from autophagy-mediated ferritin degradation in cardiomyocytes under pressure overload increases myocardial oxidative stress and develops heart failure in mice. Eur Heart J, 42(Suppl_1):ehab724.0747.

[112]ParkE, ChungSW, 2019. ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation. Cell Death Dis, 10(11):822.

[113]ParkTJ, ParkJH, LeeGS, et al., 2019. Quantitative proteomic analyses reveal that GPX4 downregulation during myocardial infarction contributes to ferroptosis in cardiomyocytes. Cell Death Dis, 10:835.

[114]PesceE, SondoE, FerreraL, et al., 2018. The autophagy inhibitor spautin-1 antagonizes rescue of mutant CFTR through an autophagy-independent and USP13-mediated mechanism. Front Pharmacol, 9:1464.

[115]PeyssonnauxC, ZinkernagelAS, SchuepbachRA, et al., 2007. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest, 117(7):1926-1932.

[116]PhilpottCC, 2020. Iron on the move: mobilizing liver iron via NCOA4. Blood, 136(23):2604-2605.

[117]PrasadMK, MohandasS, MohanramRK, 2023. Role of ferroptosis inhibitors in the management of diabetes. BioFactors, 49(2):270-296.

[118]PridhamKJ, VargheseRT, ShengZ, 2017. The role of class IA phosphatidylinositol-4,‍5-bisphosphate 3-kinase catalytic subunits in glioblastoma. Front Oncol, 7:312.

[119]ProtchenkoO, BaratzE, JadhavS, et al., 2021. Iron chaperone poly rC binding protein 1 protects mouse liver from lipid peroxidation and steatosis. Hepatology, 73(3):‍1176-1193.

[120]PuigS, Ramos-AlonsoL, RomeroAM, et al., 2017. The elemental role of iron in DNA synthesis and repair. Metallomics, 9(11):1483-1500.

[121]PullarkatV, MengZ, DonohueC, et al., 2014. Iron chelators induce autophagic cell death in multiple myeloma cells. Leuk Res, 38(8):988-996.

[122]QiRG, WangYH, BrunoPM, et al., 2017. Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer. Nat Commun, 8:2166.

[123]QinX, TangQH, JiangXJ, et al., 2020. Zinc oxide nanoparticles induce ferroptotic neuronal cell death in vitro and in vivo. Int J Nanomedicine, 15:5299-5315.

[124]QinX, ZhangJ, WangB, et al., 2021. Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells. Autophagy, 17(12):‍4266-4285.

[125]QinYH, QiaoY, WangD, et al., 2021. Ferritinophagy and ferroptosis in cardiovascular disease: mechanisms and potential applications. Biomed Pharmacother, 141:111872.

[126]ReevesAR, SansburyBE, PanMX, et al., 2021. Myeloid-specific deficiency of long-chain acyl CoA synthetase 4 reduces inflammation by remodeling phospholipids and reducing production of arachidonic acid-derived proinflammatory lipid mediators. J Immunol, 207(11):‍2744-2753.

[127]RenYF, YangMW, WangXD, et al., 2022. ELAV-like RNA binding protein 1 regulates osteogenesis in diabetic osteoporosis: involvement of divalent metal transporter 1. Mol Cell Endocrinol, 546:111559.

[128]RockfieldS, FloresI, NanjundanM, 2018. Expression and function of nuclear receptor coactivator 4 isoforms in transformed endometriotic and malignant ovarian cells. Oncotarget, 9(4):5344-5367.

[129]RyuMS, DuckKA, PhilpottCC, 2018. Ferritin iron regulators, PCBP1 and NCOA4, respond to cellular iron status in developing red cells. Blood Cells Mol Dis, 69:75-81.

[130]Santana-CodinaN, ManciasJD, 2018. The role of NCOA4-mediated ferritinophagy in health and disease. Pharmaceuticals, 11(4):114.

[131]Santana-CodinaN, GableskeS, del ReyMQ, et al., 2019. NCOA4 maintains murine erythropoiesis via cell autonomous and non-autonomous mechanisms. Haematologica, 104(7):1342-1354.

[132]Santana-CodinaN, GikandiA, ManciasJD, 2021. The role of NCOA4-mediated ferritinophagy in ferroptosis. Adv Exp Med Biol, 1301:41-57.

[133]Santana-CodinaN, del ReyMQ, KapnerKS, et al., 2022. NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron‍–‍sulfur cluster proteins. Cancer Discov, 12(9):‍2180-2197.

[134]SasazawaY, KanagakiS, TashiroE, et al., 2012. Xanthohumol impairs autophagosome maturation through direct inhibition of valosin-containing protein. ACS Chem Biol, 7(5):892-900.

[135]SavareseG, von HaehlingS, ButlerJ, et al., 2023. Iron deficiency and cardiovascular disease. Eur Heart J, 44(1):14-27.

[136]SavarynJP, ReitsmaJM, BigleyTM, et al., 2013. Human cytomegalovirus pUL29/28 and pUL38 repression of p53-regulated p21CIP1 and caspase 1 promoters during infection. J Virol, 87(5):2463-2474.

[137]SevrioukovaIF, 2011. Apoptosis-inducing factor: structure, function, and redox regulation. Antioxid Redox Signal, 14(12):2545-2579.

[138]ShiQ, LiuR, ChenL, 2022. Ferroptosis inhibitor ferrostatin‑1 alleviates homocysteine‑induced ovarian granulosa cell injury by regulating TET activity and DNA methylation. Mol Med Rep, 25(4):130.

[139]ShibataY, YasuiH, HigashikawaK, et al., 2019. Erastin, a ferroptosis-inducing agent, sensitized cancer cells to X-ray irradiation via glutathione starvation in vitro and in vivo. PLoS ONE, 14(12):e0225931.

[140]ShindoM, TorimotoY, SaitoH, et al., 2006. Functional role of DMT1 in transferrin-independent iron uptake by human hepatocyte and hepatocellular carcinoma cell, HLF. Hepatol Res, 35(3):152-162.

[141]ShizukudaY, MatobaS, MianOY, et al., 2005. Targeted disruption of p53 attenuates doxorubicin-induced cardiac toxicity in mice. Mol Cell Biochem, 273(1-2):25-32.

[142]ShroffEH, EberlinLS, DangVM, et al., 2015. MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci USA, 112(21):6539-6544.

[143]SilvaMM, de Souza-NetoFP, de JesusICG, et al., 2021. Alamandine improves cardiac remodeling induced by transverse aortic constriction in mice. Am J Physiol Heart Circ Physiol, 320(1):H352-H363.

[144]SilvainJ, ZeitouniM, ParadiesV, et al., 2021. Procedural myocardial injury, infarction and mortality in patients undergoing elective PCI: a pooled analysis of patient-level data. Eur Heart J, 42(4):323-334.

[145]SongYF, WangBC, ZhuXL, et al., 2021. Human umbilical cord blood-derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice. Cell Biol Toxicol, 37:51-64.

[146]StamenkovicA, O'HaraKA, NelsonDC, et al., 2021. Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol, 320(3):H1170-H1184.

[147]StensethK, ThybergJ, 1989. Monensin and chloroquine inhibit transfer to lysosomes of endocytosed macromolecules in cultured mouse peritoneal macrophages. Eur J Cell Biol, 49(2):326-333.

[148]SugezawaK, MorimotoM, YamamotoM, et al., 2022. GPX4 regulates tumor cell proliferation via suppressing ferroptosis and exhibits prognostic significance in gastric cancer. Anticancer Res, 42(12):5719-5729.

[149]SuiMX, XuD, ZhaoWY, et al., 2021. CIRBP promotes ferroptosis by interacting with ELAVL1 and activating ferritinophagy during renal ischaemia-reperfusion injury. J Cell Mol Med, 25(13):6203-6216.

[150]SunYM, BaoQC, XuanBQ, et al., 2018. Human cytomegalovirus protein pUL38 prevents premature cell death by binding to ubiquitin-specific protease 24 and regulating iron metabolism. J Virol, 92(13):e00191-18.

[151]TadokoroT, IkedaM, IdeT, et al., 2020. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight, 5(9):e132747.

[152]TaherAT, PorterJB, KattamisA, et al., 2016. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with nontransfusion-dependent thalassemia syndromes. Drug Des Devel Ther, 10:4073-4078.

[153]TangDL, ChenX, KangR, et al., 2021. Ferroptosis: molecular mechanisms and health implications. Cell Res, 31(2):107-125.

[154]TangLJ, LuoXJ, TuH, et al., 2021a. Ferroptosis occurs in phase of reperfusion but not ischemia in rat heart following ischemia or ischemia/reperfusion. Naunyn Schmiedebergs Arch Pharmacol, 394(2):401-410.

[155]TangLJ, ZhouYJ, XiongXM, et al., 2021b. Ubiquitin-specific protease 7 promotes ferroptosis via activation of the p53/TfR1 pathway in the rat hearts after ischemia/reperfusion. Free Radic Biol Med, 162:339-352.

[156]TangMZ, ChenZ, WuD, et al., 2018. Ferritinophagy/ferroptosis: iron-related newcomers in human diseases. J Cell Physiol, 233(12):9179-9190.

[157]TangMZ, HuangZ, LuoXL, et al., 2019. Ferritinophagy activation and sideroflexin1-dependent mitochondria iron overload is involved in apelin-13-induced cardiomyocytes hypertrophy. Free Radic Biol Med, 134:445-457.

[158]TangSC, GaoF, ChenHM, et al., 2020. The role of iron, its metabolism and ferroptosis in traumatic brain injury. Front Cell Neurosci, 14:590789.

[159]TsubouchiK, ArayaJ, YoshidaM, et al., 2019. Involvement of GPx4-regulated lipid peroxidation in idiopathic pulmonary fibrosis pathogenesis. J Immunol, 203(8):‍2076-2087.

[160]TuC, Ortega-CavaCF, WinogradP, et al., 2010. Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active src at focal adhesions. Proc Natl Acad Sci USA, 107(37):16107-16112.

[161]van BergenJMG, LiX, HuaJ, et al., 2016. Colocalization of cerebral iron with amyloid beta in mild cognitive impairment. Sci Rep, 6:35514.

[162]von HaehlingS, JankowskaEA, van VeldhuisenDJ, et al., 2015. Iron deficiency and cardiovascular disease. Nat Rev Cardiol, 12(11):659-669.

[163]WangH, JiangXJ, 2023. cGASing mitochondria to fend off ferroptosis. Cell Res, 33(4):263-264.

[164]WangK, ChenXZ, WangYH, et al., 2022. Emerging roles of ferroptosis in cardiovascular diseases. Cell Death Discov, 8:394.

[165]WangSY, WangL, QinX, et al., 2020. ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy. Signal Transduct Target Ther, 5:119.

[166]WangYQ, ZhaoYJ, YeT, et al., 2021. Ferroptosis signaling and regulators in atherosclerosis. Front Cell Dev Biol, 9:809457.

[167]WangZ, LiYN, YeYZ, et al., 2023. NLRP3 inflammasome deficiency attenuates cerebral ischemia-reperfusion injury by inhibiting ferroptosis. Brain Res Bull, 193:37-46.

[168]WuWW, SatoK, KoikeA, et al., 2010. HERC2 is an E3 ligase that targets BRCA1 for degradation. Cancer Res, 70(15):6384-6392.

[169]XiaoLL, MaXZ, YeLQ, et al., 2022. IL-9/STAT3/fatty acid oxidation-mediated lipid peroxidation contributes to Tc9 cell longevity and enhanced antitumor activity. J Clin Invest, 132(7):e153247.

[170]XieYC, HouT, LiuJY, et al., 2023. Autophagy-dependent ferroptosis as a potential treatment for glioblastoma. Front Oncol, 13:1091118.

[171]XiongHM, 2013. ZnO nanoparticles applied to bioimaging and drug delivery. Adv Mater, 25(37):5329-5335.

[172]XiongQH, LiX, LiWJ, et al., 2021. WDR45 mutation impairs the autophagic degradation of transferrin receptor and promotes ferroptosis. Front Mol Biosci, 8:645831.

[173]XiongW, WangL, YuFL, 2014. Regulation of cellular iron metabolism and its implications in lung cancer progression. Med Oncol, 31(7):28.

[174]XiuZR, ZhuYL, HanJC, et al., 2022. Caryophyllene oxide induces ferritinophagy by regulating the NCOA4/FTH1/LC3 pathway in hepatocellular carcinoma. Front Pharmacol, 13:930958.

[175]YanHF, ZouT, TuoQZ, et al., 2021. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther, 6:49.

[176]YangND, TanSH, NgS, et al., 2014. Artesunate induces cell death in human cancer cells via enhancing lysosomal function and lysosomal degradation of ferritin. J Biol Chem, 289(48):33425-33441.

[177]YangSH, WangXX, ContinoG, et al., 2011. Pancreatic cancers require autophagy for tumor growth. Genes Dev, 25(7):717-729.

[178]YangSS, LianGJ, 2020. ROS and diseases: role in metabolism and energy supply. Mol Cell Biochem, 467(1-2):1-12.

[179]YangXJ, ZhongXM, TanyiJL, et al., 2013. mir-30d Regulates multiple genes in the autophagy pathway and impairs autophagy process in human cancer cells. Biochem Biophy Res Commun, 431(3):617-622.

[180]YangXZ, LiXX, ZhangYJ, et al., 2016. Rab1 in cell signaling, cancer and other diseases. Oncogene, 35(44):‍5699-5704.

[181]YangYY, ZhangK, HuangSF, et al., 2022. Apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy. J Cell Phys, 237(4):2230-2248.

[182]YiJM, ZhuJJ, WuJ, et al., 2020. Oncogenic activation of PI3K-AKT-mToR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci USA, 117(49):31189-31197.

[183]YooSE, ChenLJ, NaR, et al., 2012. Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain. Free Radic Biol Med, 52(9):‍1820-1827.

[184]YuXX, RuanY, ShenT, et al., 2020. Dexrazoxane protects cardiomyocyte from doxorubicin-induced apoptosis by modulating miR-17-5p. BioMed Res Int, 2020:5107193.

[185]YuY, YanY, NiuFL, et al., 2021. Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases. Cell Death Discov, 7:193.

[186]ZalpoorH, AkbariA, JaziNN, et al., 2022. Possible role of autophagy induced by COVID-19 in cancer progression, chemo-resistance, and tumor recurrence. Infect Agents Cancer, 17:38.

[187]ZhangH, MaGS, YaoYY, et al., 2012. Olmesartan attenuates the impairment of endothelial cells induced by oxidized low density lipoprotein through downregulating expression of LOX-1. Int J Mol Sci, 13(2):1512-1523.

[188]ZhangHY, WangZ, LiuZX, et al., 2021. Protective effects of dexazoxane on rat ferroptosis in doxorubicin-induced cardiomyopathy through regulating HMGB1. Front Cardiovasc Med, 8:685434.

[189]ZhangJ, WangXY, GuanBY, et al., 2023. Qing-Xin-Jie-Yu Granule inhibits ferroptosis and stabilizes atherosclerotic plaques by regulating the GPX4/xCT signaling pathway. J Ethnopharmacol, 301:115852.

[190]ZhangPY, ParkHJ, ZhangJ, et al., 2020. Translation of the intrinsically disordered protein α‍-synuclein is inhibited by a small molecule targeting its structured mRNA. Proc Natl Acad Sci USA, 117(3):1457-1467.

[191]ZhaoWK, ZhouY, XuTT, et al., 2021. Ferroptosis: opportunities and challenges in myocardial ischemia-reperfusion injury. Oxid Med Cell Longev, 2021:9929687.

[192]ZhengJS, SatoM, MishimaE, et al., 2021. Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines. Cell Death Dis, 12(7):698.

[193]ZhuoXZ, WuY, NiYJ, et al., 2013. Isoproterenol instigates cardiomyocyte apoptosis and heart failure via AMPK inactivation-mediated endoplasmic reticulum stress. Apoptosis, 18(7):800-810.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE