Hub of life and death: Global regulation of ferroptosis by inter-organelle crosstalk

Yunjie Cai

1,2

Hualei Zheng

Yongyou Zhang

1,2,4,*

*Correspondence to: Yongyou Zhang, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China. E-mail: yongyouzhang@xmu.edu.cn

Ferroptosis Oxid Stress. 2026;2:202622. 10.70401/fos.2026.0039

Received: May 18, 2026Accepted: July 29, 2026Published: July 30, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Ferroptosis is an iron-dependent form of programmed cell death defined by the lethal accumulation of lipid peroxides. Accumulating evidence indicates that ferroptosis plays a critical role in a wide range of pathological processes, including tumor progression, ischemia-reperfusion injury, and neurodegenerative diseases. The key determinants of cellular susceptibility to ferroptosis are the homeostasis of iron and lipid metabolism, whose maintenance relies heavily on the precise regulation of inter-organelle communication networks. In this review, we focus on the spatial biology of ferroptosis regulation. From three core dimensions, iron homeostasis modulation, lipid metabolism remodeling, and redox balance maintenance, we systematically dissect the mechanisms by which signal crosstalk and functional coordination among multiple organelles (lysosomes, endoplasmic reticulum, mitochondria, plasma membrane, nucleus, lipid droplets, Golgi apparatus and peroxisome) govern ferroptosis initiation, signal amplification, and cellular defense responses. Comprehensive elucidation of this multi-organellar coordinated regulatory network will not only advance our fundamental understanding of ferroptosis execution but also provide a holistic perspective for the development of organelle-targeted therapeutic strategies against human diseases.

Keywords

Inter-organelle crosstalk, ferroptosis lipid peroxidation, iron metabolism, antioxidant defense system

References

1. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060-1072.

[DOI] [PubMed] [PMC]
2. Dixon SJ, Olzmann JA. The cell biology of ferroptosis. Nat Rev Mol Cell Biol. 2024;25(6):424-442.

[DOI] [PubMed] [PMC]
3. Angeli JPF, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014;16(12):1180-1191.

[DOI] [PubMed] [PMC]
4. Li Y, Ran Q, Duan Q, Jin J, Wang Y, Yu L, et al. 7-Dehydrocholesterol dictates ferroptosis sensitivity. Nature. 2024;626(7998):411-418.

[DOI] [PubMed] [PMC]
5. Agmon E, Solon J, Bassereau P, Stockwell BR. Modeling the effects of lipid peroxidation during ferroptosis on membrane properties. Sci Rep. 2018;8(1):5155.

[DOI] [PubMed] [PMC]
6. Ru Q, Li Y, Chen L, Wu Y, Min J, Wang F. Iron homeostasis and ferroptosis in human diseases: Mechanisms and therapeutic prospects. Sig Transduct Target Ther. 2024;9(1):271.

[DOI] [PubMed] [PMC]
7. Chen X, Yu C, Kang R, Tang D. Iron metabolism in ferroptosis. Front Cell Dev Biol. 2020;8:590226.

[DOI]
8. Van Renswoude J, Bridges KR, Harford JB, Klausner RD. Receptor-mediated endocytosis of transferrin and the uptake of Fe in K562 cells: Identification of a nonlysosomal acidic compartment. Proc Natl Acad Sci U S A. 1982;79(20):6186-6190.

[DOI] [PubMed] [PMC]
9. Fenton HJH. On a new reaction of tartaric acid. Chem News. 1876;33:190.
10. Sourkes TL. The discovery of lecithin, the first phospholipid. Bull Hist Chem. 2004;29(1):9-15.

[DOI]
11. Kagan VE, Mao G, Qu F, Angeli JPF, Doll S, Croix CS, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol. 2017;13(1):81-90.

[DOI]
12. Reed A, Ichu TA, Milosevich N, Melillo B, Schafroth MA, Otsuka Y, et al. LPCAT3 inhibitors remodel the polyunsaturated phospholipid content of human cells and protect from ferroptosis. ACS Chem Biol. 2022;17(6):1607-1618.

[DOI]
13. Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156(1-2):317-331.

[DOI] [PubMed] [PMC]
14. Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019;575(7784):688-692.

[DOI] [PubMed] [PMC]
15. Mao C, Liu X, Zhang Y, Lei G, Yan Y, Lee H, et al. DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature. 2021;593(7860):586-590.

[DOI] [PubMed] [PMC]
16. Kraft VAN, Bezjian CT, Pfeiffer S, Ringelstetter L, Müller C, Zandkarimi F, et al. GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling. ACS Cent Sci. 2020;6(1):41-53.

[DOI] [PubMed] [PMC]
17. Ursini F, Maiorino M, Valente M, Ferri L, Gregolin C. Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochim Biophys Acta. 1982;710(2):197-211.

[DOI] [PubMed]
18. Liu J, Lu X, Zeng S, Fu R, Wang X, Luo L, et al. ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer. Redox Biol. 2024;71:103118.

[DOI] [PubMed] [PMC]
19. Li W, Liang L, Liu S, Yi H, Zhou Y. FSP1: A key regulator of ferroptosis. Trends Mol Med. 2023;29(9):753-764.

[DOI]
20. Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019;575(7784):693-698.

[DOI] [PubMed]
21. Soula M, Weber RA, Zilka O, Alwaseem H, La K, Yen F, et al. Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers. Nat Chem Biol. 2020;16(12):1351-1360.

[DOI] [PubMed] [PMC]
22. Zheng H, Chen H, Cai Y, Shen M, Li X, Han Y, et al. Hydrogen sulfide-mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small cell lung cancer. Mol Cell. 2024;84(20):4016-4030.

[DOI] [PubMed]
23. Cañeque T, Baron L, Müller S, Carmona A, Colombeau L, Versini A, et al. Activation of lysosomal iron triggers ferroptosis in cancer. Nature. 2025;642(8067):492-500.

[DOI]
24. Xia Z, Yang X, Samovich SN, Tyurina YY, Tyurin VA, Kon N, et al. A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth suppression. Cell. 2026;189(7):1957-1974.

[DOI]
25. Liang D, Feng Y, Zandkarimi F, Wang H, Zhang Z, Kim J, et al. Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones. Cell. 2023;186(13):2748-2764.

[DOI] [PubMed] [PMC]
26. Bi G, Liang J, Bian Y, Shan G, Huang Y, Lu T, et al. Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. Nat Commun. 2024;15(1):2461.

[DOI] [PubMed] [PMC]
27. Bian Y, Shan G, Bi G, Xu Z, Liang J, Yan Y, et al. Targeting polyamine metabolism and ferroptosis enhances the efficacy of KRAS-targeted therapy depending on KEAP1 status. Nat Commun. 2025;16:9923.

[DOI]
28. Freitas FP, Alborzinia H, dos Santos AF, Nepachalovich P, Pedrera L, Zilka O, et al. 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis. Nature. 2024;626(7998):401-410.

[DOI] [PubMed]
29. Lange M, Wölk M, Li VW, Doubravsky CE, Hendricks JM, Kato S, et al. FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis. Nat Cell Biol. 2025;27(11):1902-1913.

[DOI] [PubMed] [PMC]
30. Chen F, Kang R, Tang D, Liu J. Ferroptosis: Principles and significance in health and disease. J Hematol Oncol. 2024;17(1):41.

[DOI]
31. Lambe T, Simpson RJ, Dawson S, Bouriez-Jones T, Crockford TL, Lepherd M, et al. Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism. Blood. 2009;113(8):1805-1808.

[DOI]
32. Xiao X, Moschetta GA, Xu Y, Fisher AL, Alfaro-Magallanes VM, Dev S, et al. Regulation of iron homeostasis by hepatocyte TfR1 requires HFE and contributes to hepcidin suppression in β-thalassemia. Blood. 2023;141(4):422-432.

[DOI] [PubMed] [PMC]
33. Liu X, Zhao Z, Bian Z, Benthani FA, Hu Y, Liang D, et al. Endocytosis is essential for cysteine-deprivation-induced ferroptosis. Mol Cell. 2025;85(17):3333-3342.

[DOI] [PubMed] [PMC]
34. Chen X. Lysosome: A critical hub for ferroptosis regulation. Trends Cell Biol. 2026;36(7):561-577.

[DOI] [PubMed]
35. Arosio P, Ingrassia R, Cavadini P. Ferritins: A family of molecules for iron storage, antioxidation and more. Biochim Biophys Acta. 2009;1790(7):589-599.

[DOI] [PubMed]
36. Bellelli R, Federico G, Colecchia D, Iolascon A, Chiariello M, Santoro M, et al. NCOA4 deficiency impairs systemic iron homeostasis. Cell Rep. 2016;14(3):411-421.

[DOI]
37. Hou W, Xie Y, Song X, Sun X, Lotze MT, Zeh III HJ, et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 2016;12(8):1425-1428.

[DOI] [PubMed] [PMC]
38. Mancias JD, Pontano Vaites L, Nissim S, Biancur DE, Kim AJ, Wang X, et al. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. eLife. 2015;4:e10308.

[DOI]
39. Mancias JD, Xiaoxu W, Gygi SP, Harper JW, Kimmelman AC. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature. 2014;509(7498):105-109.

[DOI]
40. Saimoto Y, Kusakabe D, Morimoto K, Matsuoka Y, Kozakura E, Kato N, et al. Lysosomal lipid peroxidation contributes to ferroptosis induction via lysosomal membrane permeabilization. Nat Commun. 2025;16(1):3554.

[DOI] [PubMed] [PMC]
41. Ubellacker JM, Tasdogan A, Ramesh V, Shen B, Mitchell EC, Martin-Sandoval MS, et al. Lymph protects metastasizing melanoma cells from ferroptosis. Nature. 2020;585(7823):113-118.

[DOI]
42. Mann J, Reznik E, Santer M, Fongheiser MA, Smith N, Hirschhorn T, et al. Ferroptosis inhibition by oleic acid mitigates iron-overload-induced injury. Cell Chem Biol. 2024;31(2):249-264.

[DOI] [PubMed] [PMC]
43. Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci U S A. 2016;113(34):E4966-E4975.

[DOI] [PubMed] [PMC]
44. Perez MA, Magtanong L, Dixon SJ, Watts JL. Dietary lipids induce ferroptosis in caenorhabditiselegans and human cancer cells. Dev Cell. 2020;54(4):447-454.

[DOI] [PubMed] [PMC]
45. Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2017;13(1):91-98.

[DOI]
46. Phadnis VV, Snider J, Varadharajan V, Ramachandiran I, Deik AA, Lai ZW, et al. MMD collaborates with ACSL4 and MBOAT7 to promote polyunsaturated phosphatidylinositol remodeling and susceptibility to ferroptosis. Cell Rep. 2023;42(9):113023.

[DOI]
47. Dixon SJ, Winter GE, Musavi LS, Lee ED, Snijder B, Rebsamen M, et al. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol. 2015;10(7):1604-1609.

[DOI] [PubMed] [PMC]
48. Von Krusenstiern AN, Robson RN, Qian N, Qiu B, Hu F, Reznik E, et al. Identification of essential sites of lipid peroxidation in ferroptosis. Nat Chem Biol. 2023;19(6):719-730.

[DOI] [PubMed] [PMC]
49. Magtanong L, Ko PJ, To M, Cao JY, Forcina GC, Tarangelo A, et al. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem Biol. 2019;26(3):420-432.

[DOI] [PubMed] [PMC]
50. Zou Y, Li H, Graham ET, Deik AA, Eaton JK, Wang W, et al. Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat Chem Biol. 2020;16(3):302-309.

[DOI] [PubMed] [PMC]
51. Yan B, Ai Y, Sun Q, Ma Y, Cao Y, Wang J, et al. Membrane damage during ferroptosis is caused by oxidation of phospholipids catalyzed by the oxidoreductases POR and CYB5R1. Mol Cell. 2021;81(2):355-369.

[DOI]
52. Chen D, Chu B, Yang X, Liu Z, Jin Y, Kon N, et al. iPLA2β-mediated lipid detoxification controls p53-driven ferroptosis independent of GPX4. Nat Commun. 2021;12:3644.

[DOI]
53. Sun WY, Tyurin VA, Mikulska-Ruminska K, Shrivastava IH, Anthonymuthu TS, Zhai YJ, et al. Phospholipase iPLA₂β averts ferroptosis by eliminating a redox lipid death signal. Nat Chem Biol. 2021;17(4):465-476.

[DOI] [PubMed] [PMC]
54. Beharier O, Tyurin VA, Goff JP, Guerrero-Santoro J, Kajiwara K, Tianjiao C, et al. PLA2G6 guards placental trophoblasts against ferroptotic injury. Proc Natl Acad Sci U S A. 2020;117(44):27319-27328.

[DOI]
55. Minikes AM, Liu P, Wang H, Hu J, Alwaseem H, Li Y, et al. HIF-independent oxygen sensing via KDM6A regulates ferroptosis. Mol Cell. 2025;85(15):2973-2987.

[DOI] [PubMed] [PMC]
56. Nguyen KT, Mun SH, Yang J, Lee J, Seok OH, Kim E, et al. The MARCHF6 E3 ubiquitin ligase acts as an NADPH sensor for the regulation of ferroptosis. Nat Cell Biol. 2022;24(8):1239-1251.

[DOI]
57. Guo J, Zhou Y, Liu D, Wang M, Wu Y, Tang D, et al. Mitochondria as multifaceted regulators of ferroptosis. Life Metab. 2022;1(2):134-148.

[DOI] [PubMed] [PMC]
58. Tang D, Chen X, Kang R, Kroemer G. Ferroptosis: Molecular mechanisms and health implications. Cell Res. 2021;31(2):107-125.

[DOI] [PubMed] [PMC]
59. Zhou Q, Meng Y, Li D, Yao L, Le J, Liu Y, et al. Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies. Sig Transduct Target Ther. 2024;9:55.

[DOI]
60. Ben Zichri-David S, Shkuri L, Ast T. Pulling back the mitochondria’s iron curtain. npj Metab Health Dis. 2025;3(1):6.

[DOI] [PubMed] [PMC]
61. She G, Hai XX, Jia LY, Zhang YJ, Ren YJ, Pang ZD, et al. Hippo pathway activation mediates cardiomyocyte ferroptosis to promote dilated cardiomyopathy through downregulating NFS1. Redox Biol. 2025;82:103597.

[DOI] [PubMed] [PMC]
62. Wang YQ, Chang SY, Wu Q, Gou YJ, Jia L, Cui YM, et al. The protective role of mitochondrial ferritin on erastin-induced ferroptosis. Front Aging Neurosci. 2016;8:308.

[DOI] [PubMed] [PMC]
63. Hassannia B, Vandenabeele P, Vanden Berghe T. Targeting ferroptosis to iron out cancer. Cancer Cell. 2019;35(6):830-849.

[DOI]
64. Thomas C, MacKey MM, Diaz AA, Cox DP. Hydroxyl radical is produced via the Fenton reaction in submitochondrial particles under oxidative stress: Implications for diseases associated with iron accumulation. Redox Rep. 2009;14(3):102-108.

[DOI] [PubMed]
65. Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB, et al. Role of mitochondria in ferroptosis. Mol Cell. 2019;73(2):354-363.

[DOI]
66. Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell. 2015;59(2):298-308.

[DOI] [PubMed] [PMC]
67. Kang YP, Mockabee-Macias A, Jiang C, Falzone A, Prieto-Farigua N, Stone E, et al. Non-canonical glutamate-cysteine ligase activity protects against ferroptosis. Cell Metab. 2021;33(1):174-189.

[DOI] [PubMed] [PMC]
68. Conlon M, Poltorack CD, Forcina GC, Armenta DA, Mallais M, Perez MA, et al. A compendium of kinetic modulatory profiles identifies ferroptosis regulators. Nat Chem Biol. 2021;17(6):665-674.

[DOI] [PubMed] [PMC]
69. Li H, Yu K, Hu H, Zhang X, Zeng S, Li J, et al. METTL17 coordinates ferroptosis and tumorigenesis by regulating mitochondrial translation in colorectal cancer. Redox Biol. 2024;71:103087.

[DOI]
70. Seibt TM, Proneth B, Conrad M. Role of GPX4 in ferroptosis and its pharmacological implication. Free Radic Biol Med. 2019;133:144-152.

[DOI] [PubMed]
71. Vasan K, Werner M, Chandel NS. Mitochondrial metabolism as a target for cancer therapy. Cell Metab. 2020;32(3):341-352.

[DOI]
72. Zhan M, Ding Y, Huang S, Liu Y, Xiao J, Yu H, et al. Lysyl oxidase-like 3 restrains mitochondrial ferroptosis to promote liver cancer chemoresistance by stabilizing dihydroorotate dehydrogenase. Nat Commun. 2023;14(1):3123.

[DOI] [PubMed] [PMC]
73. Wang H, Fleishman JS, Cheng S, Wang W, Wu F, Wang Y, et al. Retraction Note: Epigenetic modification of ferroptosis by non-coding RNAs in cancer drug resistance. Mol Cancer. 2026;25(1):109.

[DOI] [PubMed] [PMC]
74. Boukalova S, Hubackova S, Milosevic M, Ezrova Z, Neuzil J, Rohlena J. Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer. Biochim Biophys Acta Mol Basis Dis. 2020;1866(6):165759.

[DOI] [PubMed]
75. Fang JX, Uchiumi T, Yagi M, Matsumoto S, Amamoto R, Takazaki S, et al. Dihydro-orotate dehydrogenase is physically associated with the respiratory complex and its loss leads to mitochondrial dysfunction. Biosci Rep. 2013;33(2):e00021.

[DOI]
76. Yang L, An X, Yang S, Lin X, Chen Z, Xue Q, et al. The deubiquitinase USP24 suppresses ferroptosis in triple-negative breast cancer by stabilizing DHODH protein. Cell Death Dis. 2025;16(1):564.

[DOI] [PubMed] [PMC]
77. Zheng N, Li F, Huang Q, Huang X, Maj T. Macrophages and macrophage extracellular vesicles confer cancer ferroptosis resistance via PRDX6-mediated mitophagy inhibition. Redox Biol. 2025;86:103826.

[DOI] [PubMed] [PMC]
78. Yamashita SI, Sugiura Y, Matsuoka Y, Maeda R, Inoue K, Furukawa K, et al. Mitophagy mediated by BNIP3 and NIX protects against ferroptosis by downregulating mitochondrial reactive oxygen species. Cell Death Differ. 2024;31(5):651-661.

[DOI]
79. Wang X, Ma H, Sun J, Zheng T, Zhao P, Li H, et al. Mitochondrial ferritin deficiency promotes osteoblastic ferroptosis via mitophagy in type 2 diabetic osteoporosis. Biol Trace Elem Res. 2022;200(1):298-307.

[DOI] [PubMed]
80. Key J, Sen NE, Arsović A, Krämer S, Hülse R, Khan NN, et al. Systematic surveys of iron homeostasis mechanisms reveal ferritin superfamily and nucleotide surveillance regulation to be modified by PINK1 absence. Cells. 2020;9(10):2229.

[DOI] [PubMed] [PMC]
81. Sun S, Shen J, Jiang J, Wang F, Min J. Targeting ferroptosis opens new avenues for the development of novel therapeutics. Sig Transduct Target Ther. 2023;8(1):372.

[DOI] [PubMed] [PMC]
82. Pope LE, Dixon SJ. Regulation of ferroptosis by lipid metabolism. Trends Cell Biol. 2023;33(12):1077-1087.

[DOI] [PubMed] [PMC]
83. Shah R, Shchepinov MS, Pratt DA. Resolving the role of lipoxygenases in the initiation and execution of ferroptosis. ACS Cent Sci. 2018;4(3):387-396.

[DOI] [PubMed] [PMC]
84. Van Kessel ATM, Cosa G. Lipid-derived electrophiles inhibit the function of membrane channels during ferroptosis. Proc Natl Acad Sci U S A. 2024;121(21):e2317616121.

[DOI] [PubMed] [PMC]
85. Chen X, Huang J, Yu C, Liu J, Gao W, Li J, et al. A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis. Nat Commun. 2022;13:6318.

[DOI]
86. Pedrera L, Espiritu RA, Ros U, Weber J, Schmitt A, Stroh J, et al. Ferroptotic pores induce Ca²⁺ fluxes and ESCRT-III activation to modulate cell death kinetics. Cell Death Differ. 2021;28(5):1644-1657.

[DOI] [PubMed] [PMC]
87. Riegman M, Sagie L, Galed C, Levin T, Steinberg N, Dixon SJ, et al. Ferroptosis occurs through an osmotic mechanism and propagates independently of cell rupture. Nat Cell Biol. 2020;22(9):1042-1048.

[DOI] [PubMed] [PMC]
88. Hirata Y, Cai R, Volchuk A, Steinberg BE, Saito Y, Matsuzawa A, et al. Lipid peroxidation increases membrane tension, Piezo1 gating, and cation permeability to execute ferroptosis. Curr Biol. 2023;33(7):1282-1294.

[DOI]
89. Kayagaki N, Kornfeld OS, Lee BL, Stowe IB, O’Rourke K, Li Q, et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature. 2021;591(7848):131-136.

[DOI]
90. Ramos S, Hartenian E, Santos JC, Walch P, Broz P. NINJ1 induces plasma membrane rupture and release of damage-associated molecular pattern molecules during ferroptosis. EMBO J. 2024;43(7):1164-1186.

[DOI]
91. Zeng F, Chen X, Deng G. The anti-ferroptotic role of FSP1: Current molecular mechanism and therapeutic approach. Mol Biomed. 2022;3(1):37.

[DOI] [PubMed] [PMC]
92. Dai E, Meng L, Kang R, Wang X, Tang D. ESCRT-III-dependent membrane repair blocks ferroptosis. Biochem Biophys Res Commun. 2020;522(2):415-421.

[DOI] [PubMed] [PMC]
93. Stefely JA, Pagliarini DJ. Biochemistry of mitochondrial coenzyme Q biosynthesis. Trends Biochem Sci. 2017;42(10):824-843.

[DOI]
94. Crane FL. Discovery of ubiquinone (coenzyme Q) and an overview of function. Mitochondrion. 2007;7:S2-S7.

[DOI]
95. Nghiem TT, Nguyen KA, Kusuma F, Park S, Park J, Joe Y, et al. The PERK-eIF2α-ATF4 axis is involved in mediating ER-stress-induced ferroptosis via DDIT4-mTORC1 inhibition and acetaminophen-induced hepatotoxicity. Antioxidants (Basel). 2025;14(3):307.

[DOI] [PubMed] [PMC]
96. Wang H, Shi H, Rajan M, Canarie ER, Hong S, Simoneschi D, et al. FBXL5 regulates IRP2 stability in iron homeostasis via an oxygen-responsive [2Fe2S] cluster. Mol Cell. 2020;78(1):31-41.

[DOI]
97. Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama KI. The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell Metab. 2011;14(3):339-351.

[DOI]
98. Tarangelo A, Magtanong L, Bieging-Rolett KT, Li Y, Ye J, Attardi LD, et al. p53 suppresses metabolic stress-induced ferroptosis in cancer cells. Cell Rep. 2018;22(3):569-575.

[DOI] [PubMed] [PMC]
99. Zou Y, Palte MJ, Deik AA, Li H, Eaton JK, Wang W, et al. A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat Commun. 2019;10(1):1617.

[DOI] [PubMed] [PMC]
100. Yang WH, Ding CC, Sun T, Rupprecht G, Lin CC, Hsu D, et al. The hippo pathway effector TAZ regulates ferroptosis in renal cell carcinoma. Cell Rep. 2019;28(10):2501-2508.

[DOI] [PubMed] [PMC]
101. Wu J, Minikes AM, Gao M, Bian H, Li Y, Stockwell BR, et al. Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling. Nature. 2019;572(7769):402-406.

[DOI] [PubMed] [PMC]
102. Tauchi-Sato K, Ozeki S, Houjou T, Taguchi R, Fujimoto T. The surface of lipid droplets is a phospholipid monolayer with a unique Fatty Acid composition. J Biol Chem. 2002;277(46):44507-44512.

[DOI] [PubMed]
103. Olzmann JA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20(3):137-155.

[DOI] [PubMed] [PMC]
104. Dierge E, Debock E, Guilbaud C, Corbet C, Mignolet E, Mignard L, et al. Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects. Cell Metab. 2021;33(8):1701-1715.

[DOI]
105. Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, et al. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell. 2019;177(6):1522-1535.

[DOI] [PubMed]
106. Lee H, Horbath A, Kondiparthi L, Meena JK, Lei G, Dasgupta S, et al. Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance. Nat Commun. 2024;15(1):79.

[DOI] [PubMed] [PMC]
107. Zechner R, Madeo F, Kratky D. Cytosolic lipolysis and lipophagy: Two sides of the same coin. Nat Rev Mol Cell Biol. 2017;18(11):671-684.

[DOI] [PubMed]
108. Martinez-Lopez N, Singh R. Autophagy and lipid droplets in the liver. Annu Rev Nutr. 2015;35:215-237.

[DOI] [PubMed] [PMC]
109. Seo AY, Lau PW, Feliciano D, Sengupta P, Gros MAL, Cinquin B, et al. AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation. eLife. 2017;6:e21690.

[DOI] [PubMed] [PMC]
110. Schott MB, Weller SG, Schulze RJ, Krueger EW, Drizyte-Miller K, Casey CA, et al. Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes. J Cell Biol. 2019;218(10):3320-3335.

[DOI] [PubMed] [PMC]
111. Kaushik S, Cuervo AM. Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. Nat Cell Biol. 2015;17(6):759-770.

[DOI] [PubMed] [PMC]
112. Kaushik S, Cuervo AM. AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA. Autophagy. 2016;12(2):432-438.

[DOI] [PubMed] [PMC]
113. Grabner GF, Xie H, Schweiger M, Zechner R. Lipolysis: Cellular mechanisms for lipid mobilization from fat stores. Nat Metab. 2021;3(11):1445-1465.

[DOI] [PubMed]
114. Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, et al. Autophagy regulates lipid metabolism. Nature. 2009;458(7242):1131-1135.

[DOI]
115. Schott MB, Rozeveld CN, Weller SG, McNiven MA. Lipophagy at a glance. J Cell Sci. 2022;135(5):jcs259402.

[DOI]
116. Schroeder B, Schulze RJ, Weller SG, Sletten AC, Casey CA, McNiven MA. The small GTPase Rab7 as a central regulator of hepatocellular lipophagy. Hepatology. 2015;61(6):1896-1907.

[DOI] [PubMed] [PMC]
117. Mijaljica D, Prescott M, Devenish RJ. Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum. Autophagy. 2011;7(7):673-682.

[DOI] [PubMed]
118. Schulze RJ, Krueger EW, Weller SG, Johnson KM, Casey CA, Schott MB, et al. Direct lysosome-based autophagy of lipid droplets in hepatocytes. Proc Natl Acad Sci U S A. 2020;117(51):32443-32452.

[DOI] [PubMed] [PMC]
119. Alborzinia H, Ignashkova TI, Dejure FR, Gendarme M, Theobald J, Wölfl S, et al. Golgi stress mediates redox imbalance and ferroptosis in human cells. Commun Biol. 2018;1:210.

[DOI] [PubMed] [PMC]
120. Li J, Zhou Y, Li X, Yin S, Gao Y, Shang H, et al. TMEM87A suppresses ferroptosis and increases cancer immunotherapy resistance by maintaining the Golgi apparatus pH homeostasis. Nat Cancer. 2026;7(5):823-839.

[DOI] [PubMed] [PMC]
121. Gong B, Guo Y, Ding S, Liu X, Meng A, Li D, et al. A Golgi-derived vesicle potentiates PtdIns4P to PtdIns3P conversion for endosome fission. Nat Cell Biol. 2021;23(7):782-795.

[DOI] [PubMed]
122. Novales NA, Feustel KJ, He KL, Chanfreau GF, Clarke CF. Nonfunctional coq10 mutants maintain the ERMES complex and reveal true phenotypes associated with the loss of the coenzyme Q chaperone protein Coq10. J Biol Chem. 2024;300(11):107820.

[DOI] [PubMed] [PMC]
123. Ma H, Chen X, Mo S, Zhang Y, Mao X, Chen J, et al. Targeting N-glycosylation of 4F2hc mediated by glycosyltransferase B3GNT3 sensitizes ferroptosis of pancreatic ductal adenocarcinoma. Cell Death Differ. 2023;30(8):1988-2004.

[DOI]
124. Liu P, Lin C, Liu Z, Zhu C, Lin Z, Xu D, et al. Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy. Cell Mol Life Sci. 2022;79(7):352.

[DOI] [PubMed] [PMC]
125. Zou Y, Henry WS, Ricq EL, Graham ET, Phadnis VV, Maretich P, et al. Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Nature. 2020;585(7826):603-608.

[DOI] [PubMed] [PMC]
126. Cui W, Liu D, Gu W, Chu B. Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis. Cell Death Differ. 2021;28(8):2536-2551.

[DOI] [PubMed] [PMC]
127. Valm AM, Cohen S, Legant WR, Melunis J, Hershberg U, Wait E, et al. Applying systems-level spectral imaging and analysis to reveal the organelle interactome. Nature. 2017;546(7656):162-167.

[DOI] [PubMed] [PMC]
128. Prinz WA. Bridging the gap: Membrane contact sites in signaling, metabolism, and organelle dynamics. J Cell Biol. 2014;205(6):759-769.

[DOI] [PubMed] [PMC]
129. Shai N, Yifrach E, Van Roermund CWT, Cohen N, Bibi C, IJlst L, et al. Systematic mapping of contact sites reveals tethers and a function for the peroxisome-mitochondria contact. Nat Commun. 2018;9:1761.

[DOI]
130. Zhou N, Chen J, Hu M, Wen N, Cai W, Li P, et al. SLC7A11 is an unconventional H⁺ transporter in lysosomes. Cell. 2025;188(13):3441-3458.

[DOI]
131. Sheftel AD, Zhang AS, Brown C, Shirihai OS, Ponka P. Direct interorganellar transfer of iron from endosome to mitochondrion. Blood. 2007;110(1):125-132.

[DOI] [PubMed]
132. Han AP, Yu C, Lu L, Fujiwara Y, Browne C, Chin G, et al. Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. EMBO J. 2001;20(23):6909-6918.

[DOI] [PubMed] [PMC]
133. Vashisht AA, Zumbrennen KB, Huang X, Powers DN, Durazo A, Sun D, et al. Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science. 2009;326(5953):718-721.

[DOI] [PubMed] [PMC]
134. Salahudeen AA, Thompson JW, Ruiz JC, Ma HW, Kinch LN, Li Q, et al. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science. 2009;326(5953):722-726.

[DOI] [PubMed] [PMC]
135. Moroishi T, Yamauchi T, Nishiyama M, Nakayama KI. HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism. J Biol Chem. 2014;289(23):16430-16441.

[DOI]
136. Nechushtai R, Karmi O, Zuo K, Marjault HB, Darash-Yahana M, Sohn YS, et al. The balancing act of NEET proteins: Iron, ROS, calcium and metabolism. Biochim Biophys Acta Mol Cell Res. 2020;1867(11):118805.

[DOI]
137. Tamir S, Paddock ML, Darash-Yahana-Baram M, Holt SH, Sohn YS, Agranat L, et al. Structure-function analysis of NEET proteins uncovers their role as key regulators of iron and ROS homeostasis in health and disease. Biochim Biophys Acta. 2015;1853(6):1294-1315.

[DOI] [PubMed]
138. Geldenhuys WJ, Leeper TC, Carroll RT. mitoNEET as a novel drug target for mitochondrial dysfunction. Drug Discov Today. 2014;19(10):1601-1606.

[DOI] [PubMed]
139. Yuan H, Li X, Zhang X, Kang R, Tang D. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem Biophys Res Commun. 2016;478(2):838-844.

[DOI]
140. Lipper CH, Stofleth JT, Bai F, Sohn YS, Roy S, Mittler R, et al. Redox-dependent gating of VDAC by mitoNEET. Proc Natl Acad Sci U S A. 2019;116(40):19924-19929.

[DOI] [PubMed] [PMC]
141. Sasi US, Ganapathy S, Palayyan SR, Gopal RK. Mitochondria associated membranes (MAMs): Emerging drug targets for diabetes. Curr Med Chem. 2020;27(20):3362-3385.

[DOI] [PubMed]
142. Wang K, Lee CW, Sui X, Kim S, Wang S, Higgs AB, et al. The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification. Nat Commun. 2023;14(1):3533.

[DOI] [PubMed] [PMC]
143. Khandelia H, Duelund L, Pakkanen KI, Ipsen JH. Triglyceride blisters in lipid bilayers: Implications for lipid droplet biogenesis and the mobile lipid signal in cancer cell membranes. PLoS One. 2010;5(9):e12811.

[DOI] [PubMed] [PMC]
144. Duelund L, Jensen GV, Hannibal-Bach HK, Ejsing CS, Pedersen JS, Pakkanen KI, et al. Composition, structure and properties of POPC-triolein mixtures. Evidence of triglyceride domains in phospholipid bilayers. Biochim Biophys Acta. 2013;1828(8):1909-1917.

[DOI] [PubMed]
145. Mathiowetz AJ, Olzmann JA. Lipid droplets and cellular lipid flux. Nat Cell Biol. 2024;26(3):331-345.

[DOI] [PubMed] [PMC]
146. Walther TC, Kim S, Arlt H, Voth GA, Farese RV. Structure and function of lipid droplet assembly complexes. Curr Opin Struct Biol. 2023;80:102606.

[DOI]
147. Chung J, Xudong W, Lambert TJ, Lai ZW, Walther TC, Farese RV. LDAF1 and seipin form a lipid droplet assembly complex. Dev Cell. 2019;51(5):551-563.

[DOI]
148. Castro IG, Eisenberg-Bord M, Persiani E, Rochford JJ, Schuldiner M, Bohnert M. Promethin is a conserved seipin partner protein. Cells. 2019;8(3):268.

[DOI] [PubMed] [PMC]
149. You JH, Lee J, Roh JL. PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells. J Exp Clin Cancer Res. 2021;40(1):350.

[DOI] [PubMed] [PMC]
150. Bai Y, Meng L, Han L, Jia Y, Zhao Y, Gao H, et al. Lipid storage and lipophagy regulates ferroptosis. Biochem Biophys Res Commun. 2019;508(4):997-1003.

[DOI]
151. Galmes R, Houcine A, van Vliet AR, Agostinis P, Jackson CL, Giordano F. ORP5/ORP8 localize to endoplasmic reticulum-mitochondria contacts and are involved in mitochondrial function. EMBO Rep. 2016;17(6):800-810.

[DOI] [PubMed] [PMC]
152. Monteiro-Cardoso VF, Rochin L, Arora A, Houcine A, Jääskeläinen E, Kivelä AM, et al. ORP5/8 and MIB/MICOS link ER-mitochondria and intra-mitochondrial contacts for non-vesicular transport of phosphatidylserine. Cell Rep. 2022;40(12):111364.

[DOI] [PubMed]
153. Sassano ML, Tyurina YY, Diokmetzidou A, Vervoort E, Tyurin VA, More S, et al. Endoplasmic reticulum-mitochondria contacts are prime hotspots of phospholipid peroxidation driving ferroptosis. Nat Cell Biol. 2025;27(6):902-917.

[DOI] [PubMed] [PMC]
154. Shiiba I, Ito N, Oshio H, Ishikawa Y, Nagao T, Shimura H, et al. ER-mitochondria contacts mediate lipid radical transfer via RMDN3/PTPIP51 phosphorylation to reduce mitochondrial oxidative stress. Nat Commun. 2025;16:1508.

[DOI]
155. Phillips MJ, Voeltz GK. Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol. 2016;17(2):69-82.

[DOI] [PubMed] [PMC]
156. Prinz WA, Toulmay A, Balla T. The functional universe of membrane contact sites. Nat Rev Mol Cell Biol. 2020;21(1):7-24.

[DOI] [PubMed] [PMC]
157. Tao X, Zhang Y, Pang J, Liao Z, Chen G, Zhong X, et al. ER stress sensor PERK drives ferroptosis by disrupting MAMs-mediated mitochondrial homeostasis and promoting mtROS accumulation in acute myocardial infarction. Pharmacol Res. 2025;222:108029.

[DOI] [PubMed]
158. Booth DM, Várnai P, Joseph SK, Hajnóczky G. Oxidative bursts of single mitochondria mediate retrograde signaling toward the ER. Mol Cell. 2021;81(18):3866-3876.

[DOI] [PubMed] [PMC]
159. Yoboue ED, Sitia R, Simmen T. Redox crosstalk at endoplasmic reticulum (ER) membrane contact sites (MCS) uses toxic waste to deliver messages. Cell Death Dis. 2018;9(3):331.

[DOI] [PubMed] [PMC]
160. Foskett JK, White C, Cheung KH, Mak DO. Inositol trisphosphate receptor Ca²⁺ release channels. Physiol Rev. 2007;87(2):593-658.

[DOI] [PubMed] [PMC]
161. He Q, Qu M, Shen T, Su J, Xu Y, Xu C, et al. Control of mitochondria-associated endoplasmic reticulum membranes by protein S-palmitoylation: Novel therapeutic targets for neurodegenerative diseases. Ageing Res Rev. 2023;87:101920.

[DOI] [PubMed]
162. Zhang Z, Zhou H, Gu W, Wei Y, Mou S, Wang Y, et al. CGI1746 targets σ₁R to modulate ferroptosis through mitochondria-associated membranes. Nat Chem Biol. 2024;20(6):699-709.

[DOI] [PubMed]
163. De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 2011;476(7360):336-340.

[DOI] [PubMed] [PMC]
164. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature. 2011;476(7360):341-345.

[DOI] [PubMed] [PMC]
165. Duchen MR, Leyssens A, Crompton M. Transient mitochondrial depolarizations reflect focal sarcoplasmic reticular calcium release in single rat cardiomyocytes. J Cell Biol. 1998;142(4):975-988.

[DOI] [PubMed] [PMC]
166. Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J, et al. Superoxide flashes in single mitochondria. Cell. 2008;134(2):279-290.

[DOI]
167. Nakamura K, Aoyama-Ishiwatari S, Nagao T, Paaran M, Obara CJ, Sakurai-Saito Y, et al. Mitochondrial complexity is regulated at ER-mitochondria contact sites via PDZD8-FKBP8 tethering. Nat Commun. 2025;16(1):3401.

[DOI] [PubMed] [PMC]
168. Zito E. ERO1: A protein disulfide oxidase and H₂O₂ producer. Free Radic Biol Med. 2015;83:299-304.

[DOI]
169. Sevier CS, Kaiser CA. Formation and transfer of disulphide bonds in living cells. Nat Rev Mol Cell Biol. 2002;3(11):836-847.

[DOI] [PubMed]
170. Luo W, Xia B, Gong Y, Bimcle R, Yin Y. Mitochondrial and ER stress crosstalk in TBI: Mechanistic insights and therapeutic opportunities. Front Cell Neurosci. 2025;19:1697060.

[DOI]
171. Liu Y, Mao ZH, Huang J, Wang H, Zhang X, Zhou X, et al. Mitochondria-associated endoplasmic reticulum membranes in human health and diseases. MedComm. 2025;6(7):e70259.

[DOI] [PubMed] [PMC]
172. Liu Y, Huo JL, Ren K, Pan S, Liu H, Zheng Y, et al. Mitochondria-associated endoplasmic reticulum membrane (MAM): A dark horse for diabetic cardiomyopathy treatment. Cell Death Discov. 2024;10(1):148.

[DOI] [PubMed] [PMC]
173. Guerra RM, Pagliarini DJ. Coenzyme Q biochemistry and biosynthesis. Trends Biochem Sci. 2023;48(5):463-476.

[DOI] [PubMed] [PMC]
174. Deshwal S, Onishi M, Tatsuta T, Bartsch T, Cors E, Ried K, et al. Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7. Nat Cell Biol. 2023;25:246-257.

[DOI]
175. Alves F, Lane D, Nguyen TPM, Bush AI, Ayton S. In defence of ferroptosis. Sig Transduct Target Ther. 2025;10:2.

[DOI]
176. Antonenkov VD, Grunau S, Ohlmeier S, Hiltunen JK. Peroxisomes are oxidative organelles. Antioxid Redox Signal. 2010;13(4):525-537.

[DOI] [PubMed]
177. Angermüller S, Bruder G, Völkl A, Wesch H, Fahimi HD. Localization of xanthine oxidase in crystalline cores of peroxisomes. A cytochemical and biochemical study. Eur J Cell Biol. 1987;45(1):137-144.

[PubMed]
178. Islinger M, Li KW, Seitz J, Völkl A, Lüers GH. Hitchhiking of Cu/Zn superoxide dismutase to peroxisomes: Evidence for a natural piggyback import mechanism in mammals. Traffic. 2009;10(11):1711-1721.

[DOI] [PubMed]
179. Knoops B, Goemaere J, Van der Eecken V, Declercq JP. Peroxiredoxin 5: Structure, mechanism, and function of the mammalian atypical 2-Cys peroxiredoxin. Antioxid Redox Signal. 2011;15(3):817-829.

[DOI] [PubMed]
180. DiGiovanni LF, Khroud PK, Carmichael RE, Schrader TA, Gill SK, Germain K, et al. ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox. Science. 2025;389(6756):157-162.

[DOI] [PubMed]
181. Shayya HJ, Kahiapo JK, Duffié R, Lehmann KS, Bashkirova L, Monahan K, et al. ER stress transforms random olfactory receptor choice into axon targeting precision. Cell. 2022;185(21):3896-3912.

[DOI] [PubMed] [PMC]
182. Zhang D, Liu Y, Zhu Y, Zhang Q, Guan H, Liu S, et al. A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis. Nat Cell Biol. 2022;24(5):766-782.

[DOI] [PubMed]
183. He F, Zhang P, Liu J, Wang R, Kaufman RJ, Yaden BC, et al. ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis. J Hepatol. 2023;79(2):362-377.

[DOI]
184. Smolková K, Mikó E, Kovács T, Leguina-Ruzzi A, Sipos A, Bai P. Nuclear factor erythroid 2-related factor 2 in regulating cancer metabolism. Antioxid Redox Signal. 2020;33(13):966-997.

[DOI]
185. Koppula P, Zhang Y, Zhuang L, Gan B. Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun. 2018;38:12.

[DOI]
186. Mai TT, Hamaï A, Hienzsch A, Cañeque T, Müller S, Wicinski J, et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem. 2017;9(10):1025-1033.

[DOI] [PubMed] [PMC]
187. Gong R, Wan X, Jiang S, Guan Y, Li Y, Jiang T, et al. GPX4-AUTAC induces ferroptosis in breast cancer by promoting the selective autophagic degradation of GPX4 mediated by TRAF6-p62. Cell Death Differ. 2025;32(11):2022-2037.

[DOI] [PubMed] [PMC]
188. Natale R, Wheeler R, Moore M, Dallaire B, Lynch W, Carlson R, et al. Multicenter phase II trial of brequinar sodium in patients with advanced melanoma. Ann Oncol. 1992;3(8):659-660.

[DOI] [PubMed]
189. White RM, Cech J, Ratanasirintrawoot S, Lin CY, Rahl PB, Burke CJ, et al. DHODH modulates transcriptional elongation in the neural crest and melanoma. Nature. 2011;471(7339):518-522.

[DOI] [PubMed] [PMC]
190. Urba S, Doroshow J, Cripps C, Robert F, Velez-Garcia E, Dallaire B, et al. Multicenter phase II trial of brequinar sodium in patients with advanced squamous-cell carcinoma of the head and neck. Cancer Chemother Pharmacol. 1992;31(2):167-169.

[DOI] [PubMed]
191. Maroun J, Ruckdeschel J, Natale R, Morgan R, Dallaire B, Sisk R, et al. Multicenter phase II study of brequinar sodium in patients with advanced lung cancer. Cancer Chemother Pharmacol. 1993;32(1):64-66.

[DOI]
192. Li L, Ng SR, Colón CI, Drapkin BJ, Hsu PP, Zhaoqi L, et al. Identification of DHODH as a therapeutic target in small cell lung cancer. Sci Transl Med. 2019;11(517):eaaw7852.

[DOI]
193. Sykes DB, Kfoury YS, Mercier FE, Wawer MJ, Law JM, Haynes MK, et al. Inhibition of dihydroorotate dehydrogenase overcomes differentiation blockade in acute myeloid leukemia. Cell. 2016;167(1):171-186.

[DOI] [PubMed] [PMC]
194. Brown KK, Spinelli JB, Asara JM, Toker A. Adaptive reprogramming of de novo pyrimidine synthesis is a metabolic vulnerability in triple-negative breast cancer. Cancer Discov. 2017;7(4):391-399.

[DOI] [PubMed] [PMC]
195. Mathur D, Stratikopoulos E, Ozturk S, Steinbach N, Pegno S, Schoenfeld S, et al. PTEN regulates glutamine flux to pyrimidine synthesis and sensitivity to dihydroorotate dehydrogenase inhibition. Cancer Discov. 2017;7(4):380-390.

[DOI] [PubMed] [PMC]
196. Wang X, Yang K, Wu Q, Kim LJY, Morton AR, Gimple RC, et al. Targeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells. Sci Transl Med. 2019;11(504):eaau4972.

[DOI] [PubMed] [PMC]
197. Hosseini M, Dousset L, Mahfouf W, Serrano-Sanchez M, Redonnet-Vernhet I, Mesli S, et al. Energy metabolism rewiring precedes UVB-induced primary skin tumor formation. Cell Rep. 2018;23(12):3621-3634.

[DOI] [PubMed]
198. Ichikawa Y, Ghanefar M, Bayeva M, Wu R, Khechaduri A, Prasad SVN, et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest. 2014;124(2):617-630.

[DOI] [PubMed] [PMC]
199. Zuris JA, Harir Y, Conlan AR, Shvartsman M, Michaeli D, Tamir S, et al. Facile transfer of [2Fe-2S] clusters from the diabetes drug target mitoNEET to an apo-acceptor protein. Proc Natl Acad Sci U S A. 2011;108(32):13047-13052.

[DOI] [PubMed] [PMC]
200. Tamir S, Zuris JA, Agranat L, Lipper CH, Conlan AR, Michaeli D, et al. Nutrient-deprivation autophagy factor-1 (NAF-1): Biochemical properties of a novel cellular target for anti-diabetic drugs. PLoS One. 2013;8(5):e61202.

[DOI] [PubMed] [PMC]
201. Li W, Yang J, Luo L, Jiang M, Qin B, Yin H, et al. Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death. Nat Commun. 2019;10(1):3349.

[DOI] [PubMed] [PMC]
202. Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife. 2014;3:e02523.

[DOI] [PubMed] [PMC]
203. Louandre C, Ezzoukhry Z, Godin C, Barbare JC, Mazière JC, Chauffert B, et al. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib. Int J Cancer. 2013;133(7):1732-1742.

[DOI] [PubMed]
204. Lachaier E, Louandre C, Godin C, Saidak Z, Baert M, Diouf M, et al. Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors. Anticancer Res. 2014;34(11):6417-6422.

[PubMed]
205. Hendricks JM, Doubravsky CE, Wehri E, Li Z, Roberts MA, Deol KK, et al. Identification of structurally diverse FSP1 inhibitors that sensitize cancer cells to ferroptosis. Cell Chem Biol. 2023;30(9):1090-1103.

[DOI] [PubMed] [PMC]
206. Nakamura T, Hipp C, Santos Dias Mourão A, Borggräfe J, Aldrovandi M, Henkelmann B, et al. Phase separation of FSP1 promotes ferroptosis. Nature. 2023;619(7969):371-377.

[DOI]
207. Selim M, Foster LD, Moy CS, Xi G, Hill MD, Morgenstern LB, et al. Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): A multicentre, randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 2019;18(5):428-438.

[DOI] [PubMed] [PMC]
208. Foster L, Robinson L, Yeatts SD, Conwit RA, Shehadah A, Lioutas V, et al. Effect of deferoxamine on trajectory of recovery after intracerebral hemorrhage: A post hoc analysis of the i-DEF trial. Stroke. 2022;53(7):2204-2210.

[DOI] [PubMed] [PMC]
209. Wang G, Hu W, Tang Q, Wang L, Sun XG, Chen Y, et al. Effect comparison of both iron chelators on outcomes, iron deposit, and iron transporters after intracerebral hemorrhage in rats. Mol Neurobiol. 2016;53(6):3576-3585.

[DOI] [PubMed]
210. Feng Y, Madungwe NB, Imam Aliagan AD, Tombo N, Bopassa JC. Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels. Biochem Biophys Res Commun. 2019;520(3):606-611.

[DOI]
211. Wang Z, Yao M, Jiang L, Wang L, Yang Y, Wang Q, et al. Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis. Biomed Pharmacother. 2022;154:113572.

[DOI] [PubMed]
212. Sun F, He Y, Yang Z, Xu G, Wang R, Juan Z, et al. Propofol pretreatment inhibits ferroptosis and alleviates myocardial ischemia-reperfusion injury through the SLC16A13-AMPK-GPX4 pathway. Biomed Pharmacother. 2024;179:117345.

[DOI] [PubMed]
213. Liu R, Li F, Hao S, Hou D, Zeng X, Huang H, et al. Low-dose Olaparib improves septic cardiac function by reducing ferroptosis via accelerated mitophagy flux. Pharmacol Res. 2024;200:107056.

[DOI] [PubMed]
214. McLachlan DRC, Kruck TPA, Kalow W, Andrews DF, Dalton AJ, Bell MY, et al. Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet. 1991;337(8753):1304-1308.

[DOI]
215. Devos D, Labreuche J, Rascol O, Corvol JC, Duhamel A, Guyon Delannoy P, et al. Trial of deferiprone in Parkinson’s disease. N Engl J Med. 2022;387(22):2045-2055.

[DOI] [PubMed]
216. Witzel S, Maier A, Steinbach R, Grosskreutz J, Koch JC, Sarikidi A, et al. Safety and effectiveness of long-term intravenous administration of edaravone for treatment of patients with amyotrophic lateral sclerosis. JAMA Neurol. 2022;79(2):121-130.

[DOI] [PubMed] [PMC]
217. Kaufmann P, Thompson JLP, Levy G, Buchsbaum R, Shefner J, Krivickas LS, et al. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Ann Neurol. 2009;66(2):235-244.

[DOI] [PubMed] [PMC]
218. Conrad M, Pratt DA. The chemical basis of ferroptosis. Nat Chem Biol. 2019;15(12):1137-1147.

[DOI]
219. Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 2022;22(7):381-396.

[DOI] [PubMed] [PMC]
220. Heneka MT, Fink A, Doblhammer G. Effect of pioglitazone medication on the incidence of dementia. Ann Neurol. 2015;78(2):284-294.

[DOI]
221. Liu Y, Zhao D, Yang F, Ye C, Chen Z, Chen Y, et al. In situ self-assembled phytopolyphenol-coordinated intelligent nanotherapeutics for multipronged management of ferroptosis-driven Alzheimer’s disease. ACS Nano. 2024;18(11):7890-7906.

[DOI] [PubMed]
222. Moorthy H, Ramesh M, Padhi D, Baruah P, Govindaraju T. Polycatechols inhibit ferroptosis and modulate tau liquid-liquid phase separation to mitigate Alzheimer’s disease. Mater Horiz. 2024;11(13):3082-3089.

[DOI] [PubMed]

Copyright

© The Author(s) 2026. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Publisher’s Note

Science Exploration remains a neutral stance on jurisdictional claims in published maps and institutional affiliations. The views expressed in this article are solely those of the author(s) and do not reflect the opinions of the Editors or the publisher.

Share And Cite

Science Exploration Style

Cai Y, Zheng H, Zhang Y. Hub of life and death: Global regulation of ferroptosis by inter-organelle crosstalk. Ferroptosis Oxid Stress. 2026;2:202622. https://doi.org/10.70401/fos.2026.0039

Copy completed.

Submit a Manuscript

Author Instructions

Cite this Article

Download

Download PDF

Download XML

Export Citation

RIS

BibTex

EndNote

Article Metrics

View

Download

Cited

Article Updates

Sections

Abstract
Keywords
References
Copyright

Get citation

Share Link

copy

First Name:*

Please fill in the content.

Last Name:*

Please fill in the content.

Email:*

Please fill in the content.

Ferroptosis and Oxidative Stress

Hub of life and death: Global regulation of ferroptosis by inter-organelle crosstalk

Yunjie Cai

Hualei Zheng

Yongyou Zhang

Abstract

Keywords

References

Copyright

Publisher’s Note

Share And Cite

Science Exploration Style

Download

Export Citation

Article Metrics

Article Updates

Contents

Share Link

Subscribe

Ferroptosis and Oxidative Stress

Navigation

Follow us

Ferroptosis and Oxidative Stress

Hub of life and death: Global regulation of ferroptosis by inter-organelle crosstalk

Yunjie Cai

Hualei Zheng

Yongyou Zhang

Abstract

Keywords

References

Copyright

Publisher’s Note

Share And Cite

Science Exploration Style

Download

Export Citation

Article Metrics

Article Updates

Related Articles

Contents

Science Exploration Style

Share Link

Subscribe

Ferroptosis and Oxidative Stress

Navigation

Follow us