1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Nutrition
  4. Volume 42, 2022
  5. Article

Annual Review of Nutrition

Volume 42, 2022

Nutritional and Metabolic Control of Ferroptosis

Abstract

Ferroptosis is a type of regulated cell death characterized by an excessive lipid peroxidation of cellular membranes caused by the disruption of the antioxidant defense system and/or an imbalanced cellular metabolism. Ferroptosis differentiates from other forms of regulated cell death in that several metabolic pathways and nutritional aspects, including endogenous antioxidants (such as coenzyme Q, vitamin E, and di/tetrahydrobiopterin), iron handling, energy sensing, selenium utilization, amino acids, and fatty acids, directly regulate the cells’ sensitivity to lipid peroxidation and ferroptosis. As hallmarks of ferroptosis have been documented in a variety of diseases, including neurodegeneration, acute organ injury, and therapy-resistant tumors, the modulation of ferroptosis using pharmacological tools or by metabolic reprogramming holds great potential for the treatment of ferroptosis-associated diseases and cancer therapy. Hence, this review focuses on the regulation of ferroptosis by metabolic and nutritional cues and discusses the potential of nutritional interventions for therapy by targeting ferroptosis.

Keyword(s): coenzyme Q10, FSP1, GPX4, lipid peroxidation, PUFA, regulated necrotic cell death
Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-062320-114541
2022-08-22
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/nutr/42/1/annurev-nutr-062320-114541.html?itemId=/content/journals/10.1146/annurev-nutr-062320-114541&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Abrams RP, Carroll WL, Woerpel KA. 2016. Five-membered ring peroxide selectively initiates ferroptosis in cancer cells. ACS Chem. Biol. 11:1305–12
     [Google Scholar]
  2. 2.
    Aldrovandi M, Fedorova M, Conrad M 2021. Juggling with lipids, a game of Russian roulette. Trends Endocrinol. Metab. 32:463–73
     [Google Scholar]
  3. 3.
    Alim I, Caulfield JT, Chen Y, Swarup V, Geschwind DH et al. 2019. Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell 177:1262–79.e25
     [Google Scholar]
  4. 4.
    Altamura S, Vegi NM, Hoppe PS, Schroeder T, Aichler M et al. 2020. Glutathione peroxidase 4 and vitamin E control reticulocyte maturation, stress erythropoiesis and iron homeostasis. Haematologica 105:937–50
     [Google Scholar]
  5. 5.
    Anandhan A, Dodson M, Schmidlin CJ, Liu P, Zhang DD. 2020. Breakdown of an ironclad defense system: the critical role of NRF2 in mediating ferroptosis. Cell Chem. Biol. 27:436–47
     [Google Scholar]
  6. 6.
    Anderson GJ, Vulpe CD. 2009. Mammalian iron transport. Cell. Mol. Life Sci. 66:3241–61
     [Google Scholar]
  7. 7.
    Anegawa D, Sugiura Y, Matsuoka Y, Sone M, Shichiri M et al. 2021. Hepatic resistance to cold ferroptosis in a mammalian hibernator Syrian hamster depends on effective storage of diet-derived α-tocopherol. Commun. Biol. 4:796
     [Google Scholar]
  8. 8.
    Ashraf A, So PW. 2020. Spotlight on ferroptosis: iron-dependent cell death in Alzheimer's disease. Front. . Aging Neurosci. 12:196
     [Google Scholar]
  9. 9.
    Augustin Y, Staines HM, Krishna S 2020. Artemisinins as a novel anti-cancer therapy: targeting a global cancer pandemic through drug repurposing. Pharmacol. Ther. 216:107706
     [Google Scholar]
  10. 10.
    Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ et al. 2020. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science 368:85–89
     [Google Scholar]
  11. 11.
    Bannai S, Tsukeda H, Okumura H. 1977. Effect of antioxidants on cultured human diploid fibroblasts exposed to cystine-free medium. Biochem. Biophys. Res. Commun. 74:1582–88
     [Google Scholar]
  12. 12.
    Bast A, Brenninkmeijer JW, Savenije-Chapel EM, Noordhoek J. 1983. Cytochrome P450 oxidase activity and its role in NADPH dependent lipid peroxidation. FEBS Lett. 151:185–88
     [Google Scholar]
  13. 13.
    Beatty A, Singh T, Tyurina YY, Tyurin VA, Samovich S et al. 2021. Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. Nat. Commun. 12:2244
     [Google Scholar]
  14. 14.
    Beharier O, Tyurin VA, Goff JP, Guerrero-Santoro J, Kajiwara K et al. 2020. PLA2G6 guards placental trophoblasts against ferroptotic injury. PNAS 117:27319–28
     [Google Scholar]
  15. 15.
    Belaidi AA, Bush AI. 2016. Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics. J. Neurochem. 139:Suppl. 1179–97
     [Google Scholar]
  16. 16.
    Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B et al. 2019. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575:688–92
     [Google Scholar]
  17. 17.
    Bieri JG. 1959. An effect of selenium and cystine on lipide peroxidation in tissues deficient in vitamin E. Nature 184:Suppl. 151148–49
     [Google Scholar]
  18. 18.
    Blomme A, Ford CA, Mui E, Patel R, Ntala C et al. 2020. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat. Commun. 11:2508
     [Google Scholar]
  19. 19.
    Boa AN, Canavan SP, Hirst PR, Ramsey C, Stead AM, McConkey GA. 2005. Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase. Bioorg. Med. Chem. 13:1945–67
     [Google Scholar]
  20. 20.
    Bogacz M, Krauth-Siegel RL 2018. Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death. Elife 7:e37503
     [Google Scholar]
  21. 21.
    Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y. 2016. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem. Sci. 41:274–86
     [Google Scholar]
  22. 22.
    Bosl MR, Takaku K, Oshima M, Nishimura S, Taketo MM. 1997. Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene (Trsp). PNAS 94:5531–34
     [Google Scholar]
  23. 23.
    Brielmeier M, Bechet JM, Suppmann S, Conrad M, Laux G, Bornkamm GW. 2001. Cloning of phospholipid hydroperoxide glutathione peroxidase (PHGPx) as an anti-apoptotic and growth promoting gene of Burkitt lymphoma cells. Biofactors 14:179–90
     [Google Scholar]
  24. 24.
    Brown CW, Amante JJ, Chhoy P, Elaimy AL, Liu H et al. 2019. Prominin2 drives ferroptosis resistance by stimulating iron export. Dev. Cell 51:575–86.e4
     [Google Scholar]
  25. 25.
    Brown CW, Amante JJ, Goel HL, Mercurio AM. 2017. The α6β4 integrin promotes resistance to ferroptosis. J. Cell Biol. 216:4287–97
     [Google Scholar]
  26. 26.
    Brown CW, Chhoy P, Mukhopadhyay D, Karner ER, Mercurio AM. 2021. Targeting prominin2 transcription to overcome ferroptosis resistance in cancer. EMBO Mol. Med. 13:e13792
     [Google Scholar]
  27. 27.
    Conrad M, Kagan VE, Bayir H, Pagnussat GC, Head Bet al 2018. Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev 32:9–10602–19
     [Google Scholar]
  28. 28.
    Canli O, Alankus YB, Grootjans S, Vegi N, Hultner L et al. 2016. Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors. Blood 127:139–48
     [Google Scholar]
  29. 29.
    Cao J, Chen X, Jiang L, Lu B, Yuan M et al. 2020. DJ-1 suppresses ferroptosis through preserving the activity of S-adenosyl homocysteine hydrolase. Nat. Commun. 11:1251
     [Google Scholar]
  30. 30.
    Cao X. 2020. COVID-19: immunopathology and its implications for therapy. Nat. Rev. Immunol. 20:269–70
     [Google Scholar]
  31. 31.
    Carlson BA, Tobe R, Yefremova E, Tsuji PA, Hoffmann VJ et al. 2016. Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. Redox. Biol. 9:22–31
     [Google Scholar]
  32. 32.
    Chen D, Chu B, Yang X, Liu Z, Jin Y et al. 2021. iPLA2β-mediated lipid detoxification controls p53-driven ferroptosis independent of GPX4. Nat. Commun. 12:3644
     [Google Scholar]
  33. 33.
    Chen GQ, Benthani FA, Wu J, Liang D, Bian ZX, Jiang X. 2020. Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis. Cell Death Differ. 27:242–54
     [Google Scholar]
  34. 34.
    Chen L, Hambright WS, Na R, Ran Q 2015. Ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis. J. Biol. Chem. 290:28097–106
     [Google Scholar]
  35. 35.
    Chen Y, Fan H, Wang S, Tang G, Zhai C, Shen L. 2021. Ferroptosis: a novel therapeutic target for ischemia-reperfusion injury. Front. Cell Dev. Biol. 9:688605
     [Google Scholar]
  36. 36.
    Chorley BN, Campbell MR, Wang X, Karaca M, Sambandan D et al. 2012. Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha. Nucleic. Acids. Res. 40:7416–29
     [Google Scholar]
  37. 37.
    Christidi E, Brunham LR. 2021. Regulated cell death pathways in doxorubicin-induced cardiotoxicity. Cell Death. Dis. 12:339
     [Google Scholar]
  38. 38.
    Conlon M, Poltorack CD, Forcina GC, Armenta DA, Mallais M et al. 2021. A compendium of kinetic modulatory profiles identifies ferroptosis regulators. Nat. Chem. Biol. 17:665–74
     [Google Scholar]
  39. 39.
    Imai H, Hakkaku N, Iwamoto R, Suzuki J, Suzuki Tet al 2009. Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice. J. Biol. Chem 284:4732522–32
     [Google Scholar]
  40. 40.
    Conrad M, Pratt DA. 2019. The chemical basis of ferroptosis. Nat. Chem. Biol. 15:1137–47
     [Google Scholar]
  41. 41.
    Deleted in proof
  42. 42.
    Conrad M, Proneth B. 2020. Selenium: tracing another essential element of ferroptotic cell death. Cell Chem. Biol. 27:409–19
     [Google Scholar]
  43. 43.
    Cui W, Liu D, Gu W, Chu B. 2021. Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis. Cell Death Differ. 28:2536–51
     [Google Scholar]
  44. 44.
    Dangol S, Chen Y, Hwang BK, Jwa NS. 2019. Iron- and reactive oxygen species-dependent ferroptotic cell death in rice-magnaporthe oryzae interactions. Plant Cell 31:189–209
     [Google Scholar]
  45. 45.
    Dar HH, Anthonymuthu TS, Ponomareva LA, Souryavong AB, Shurin GV et al. 2021. A new thiol-independent mechanism of epithelial host defense against Pseudomonas aeruginosa: iNOS/NO· sabotage of theft-ferroptosis. Redox. Biol. 45:102045
     [Google Scholar]
  46. 46.
    Dar HH, Tyurina YY, Mikulska-Ruminska K, Shrivastava I, Ting HC et al. 2018. Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium. J. Clin. Investig. 128:4639–53
     [Google Scholar]
  47. 47.
    de Vries RJ, Tessier SN, Banik PD, Nagpal S, Cronin SEJ et al. 2019. Supercooling extends preservation time of human livers. Nat. Biotechnol. 37:1131–36
     [Google Scholar]
  48. 48.
    Dierge E, Debock E, Guilbaud C, Corbet C, Mignolet E et al. 2021. Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects. Cell Metab. 33:1701–15.e5
     [Google Scholar]
  49. 49.
    Ding CC, Rose J, Sun T, Wu J, Chen PH et al. 2020. MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis. Nat. Metab. 2:270–77
     [Google Scholar]
  50. 50.
    Distefano AM, Martin MV, Cordoba JP, Bellido AM, D'Ippolito S et al. 2017. Heat stress induces ferroptosis-like cell death in plants. J. Cell Biol. 216:463–76
     [Google Scholar]
  51. 51.
    Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM et al. 2012. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–72
     [Google Scholar]
  52. 52.
    Dixon SJ, Winter GE, Musavi LS, Lee ED, Snijder B et al. 2015. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem. Biol. 10:1604–9
     [Google Scholar]
  53. 53.
    Dodson M, Castro-Portuguez R, Zhang DD. 2019. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox. Biol. 23:101107
     [Google Scholar]
  54. 54.
    Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC et al. 2019. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575:693–98
     [Google Scholar]
  55. 55.
    Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S et al. 2017. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat. Chem. Biol. 13:91–98
     [Google Scholar]
  56. 56.
    Du J, Zhou Y, Li Y, Xia J, Chen Y et al. 2020. Identification of Frataxin as a regulator of ferroptosis. Redox. Biol. 32:101483
     [Google Scholar]
  57. 57.
    Eagle H. 1955. Nutrition needs of mammalian cells in tissue culture. Science 122:501–14
     [Google Scholar]
  58. 58.
    Eagle H, Piez KA, Oyama VI. 1961. The biosynthesis of cystine in human cell cultures. J. Biol. Chem. 236:1425–28
     [Google Scholar]
  59. 59.
    Eaton JK, Furst L, Ruberto RA, Moosmayer D, Hilpmann A et al. 2020. Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles. Nat. Chem. Biol. 16:497–506
     [Google Scholar]
  60. 60.
    Elguindy MM, Nakamaru-Ogiso E. 2015. Apoptosis-inducing factor (AIF) and its family member protein, AMID, are rotenone-sensitive NADH:ubiquinone oxidoreductases (NDH-2). J. Biol. Chem. 290:20815–26
     [Google Scholar]
  61. 61.
    Evans DR, Guy HI. 2004. Mammalian pyrimidine biosynthesis: fresh insights into an ancient pathway. J. Biol. Chem. 279:33035–38
     [Google Scholar]
  62. 62.
    Fang X, Cai Z, Wang H, Han D, Cheng Q et al. 2020. Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ. Res. 127:486–501
     [Google Scholar]
  63. 63.
    Fang X, Wang H, Han D, Xie E, Yang X et al. 2019. Ferroptosis as a target for protection against cardiomyopathy. PNAS 116:2672–80
     [Google Scholar]
  64. 64.
    Feng H, Schorpp K, Jin J, Yozwiak CE, Hoffstrom BG et al. 2020. Transferrin receptor is a specific ferroptosis marker. Cell Rep. 30:3411–23.e7
     [Google Scholar]
  65. 65.
    Feng Y, Madungwe NB, Imam Aliagan AD, Tombo N, Bopassa JC. 2019. Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels. Biochem. Biophys. Res. Commun. 520:606–11
     [Google Scholar]
  66. 66.
    Friedmann Angeli JP, Conrad M 2018. Selenium and GPX4, a vital symbiosis. Free Radic. Biol. Med. 127:153–59
     [Google Scholar]
  67. 67.
    Friedmann Angeli JP, Florencio Porto F, Palina N, Lohans P, Omkar Z et al. 2021. 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis. Prepr. Version 1, Research Square. https://doi.org/10.21203/rs.3.rs-943221/v1
    [Crossref]
  68. 68.
    Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA et al. 2014. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol. 16:1180–91
     [Google Scholar]
  69. 69.
    Gai C, Yu M, Li Z, Wang Y, Ding D et al. 2020. Acetaminophen sensitizing erastin-induced ferroptosis via modulation of Nrf2/heme oxygenase-1 signaling pathway in non-small-cell lung cancer. J. Cell. Physiol. 235:3329–39
     [Google Scholar]
  70. 70.
    Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D et al. 2018. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 25:486–541
     [Google Scholar]
  71. 71.
    Chen Y, Liu Y, Lan T, Qin W, Zhu YTet al 2018. Quantitative profiling of protein carbonylations in ferroptosis by an aniline-derived probe. J. Am. Chem. Soc 140:134712–20
     [Google Scholar]
  72. 72.
    Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X. 2016. Ferroptosis is an autophagic cell death process. Cell Res. 26:1021–32
     [Google Scholar]
  73. 73.
    Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. 2015. Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell 59:298–308
     [Google Scholar]
  74. 74.
    Gao M, Yi J, Zhu J, Minikes AM, Monian P et al. 2019. Role of mitochondria in ferroptosis. Mol. Cell 73:354–63.e3
     [Google Scholar]
  75. 75.
    Garcia-Bermudez J, Baudrier L, Bayraktar EC, Shen Y, La K et al. 2019. Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death. Nature 567:118–22
     [Google Scholar]
  76. 76.
    Gaschler MM, Andia AA, Liu H, Csuka JM, Hurlocker B et al. 2018. FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat. Chem. Biol. 14:507–15
     [Google Scholar]
  77. 77.
    Gaschler MM, Hu F, Feng H, Linkermann A, Min W, Stockwell BR 2018. Determination of the subcellular localization and mechanism of action of ferrostatins in suppressing ferroptosis. ACS Chem. Biol. 13:1013–20
     [Google Scholar]
  78. 78.
    Geng N, Shi BJ, Li SL, Zhong ZY, Li YC et al. 2018. Knockdown of ferroportin accelerates erastin-induced ferroptosis in neuroblastoma cells. Eur. Rev. Med. Pharmacol. Sci. 22:3826–36
     [Google Scholar]
  79. 79.
    Hall ED. 1992. Novel inhibitors of iron-dependent lipid peroxidation for neurodegenerative disorders. Ann. Neurol. 32:Suppl. S137–42
     [Google Scholar]
  80. 80.
    Hambright WS, Fonseca RS, Chen L, Na R, Ran Q. 2017. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox. Biol. 12:8–17
     [Google Scholar]
  81. 81.
    Hangauer MJ, Viswanathan VS, Ryan MJ, Bole D, Eaton JK et al. 2017. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature 551:247–50
     [Google Scholar]
  82. 82.
    Hattori K, Ishikawa H, Sakauchi C, Takayanagi S, Naguro I, Ichijo H. 2017. Cold stress-induced ferroptosis involves the ASK1-p38 pathway. EMBO Rep. 18:2067–78
     [Google Scholar]
  83. 83.
    Hayano M, Yang WS, Corn CK, Pagano NC, Stockwell BR. 2016. Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ. 23:270–78
     [Google Scholar]
  84. 84.
    Herraiz T, Galisteo J. 2004. Endogenous and dietary indoles: a class of antioxidants and radical scavengers in the ABTS assay. Free Radic. Res. 38:323–31
     [Google Scholar]
  85. 85.
    Hinman A, Holst CR, Latham JC, Bruegger JJ, Ulas G et al. 2018. Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. PLOS ONE 13:e0201369
     [Google Scholar]
  86. 86.
    Hirschhorn T, Stockwell BR. 2019. The development of the concept of ferroptosis. Free Radic. Biol. Med. 133:130–43
     [Google Scholar]
  87. 87.
    Homma T, Kobayashi S, Conrad M, Konno H, Yokoyama C, Fujii J. 2021. Nitric oxide protects against ferroptosis by aborting the lipid peroxidation chain reaction. Nitric Oxide 115:34–43
     [Google Scholar]
  88. 88.
    Homma T, Kobayashi S, Sato H, Fujii J. 2019. Edaravone, a free radical scavenger, protects against ferroptotic cell death in vitro. Exp. Cell Res. 384:111592
     [Google Scholar]
  89. 89.
    Hou W, Xie Y, Song X, Sun X, Lotze MT et al. 2016. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12:1425–28
     [Google Scholar]
  90. 90.
    Ibar C, Irvine KD. 2020. Integration of Hippo-YAP signaling with metabolism. Dev. Cell 54:256–67
     [Google Scholar]
  91. 91.
    Ide S, Kobayashi Y, Ide K, Strausser SA, Abe K et al. 2021. Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair. Elife 10:e68603
     [Google Scholar]
  92. 92.
    Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G et al. 2018. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell 172:409–22.e21
     [Google Scholar]
  93. 93.
    Ingold KU, Pratt DA. 2014. Advances in radical-trapping antioxidant chemistry in the 21st century: a kinetics and mechanisms perspective. Chem. Rev. 114:9022–46
     [Google Scholar]
  94. 94.
    Ishii T, Bannai S, Sugita Y. 1981. Mechanism of growth stimulation of L1210 cells by 2-mercaptoethanol in vitro. Role of the mixed disulfide of 2-mercaptoethanol and cysteine. J. Biol. Chem. 256:12387–92
     [Google Scholar]
  95. 95.
    Jacobs W, Lammens M, Kerckhofs A, Voets E, Van San E et al. 2020. Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID-19): Autopsy reveals a ferroptosis signature. ESC Heart Fail. 7:3772–81
     [Google Scholar]
  96. 96.
    Jakaria M, Belaidi AA, Bush AI, Ayton S. 2021. Ferroptosis as a mechanism of neurodegeneration in Alzheimer's disease. J. Neurochem. 159:804–25
     [Google Scholar]
  97. 97.
    Jiang L, Kon N, Li T, Wang SJ, Su T et al. 2015. Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520:57–62
     [Google Scholar]
  98. 98.
    Jiang X, Stockwell BR, Conrad M 2021. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell Biol. 22:266–82
     [Google Scholar]
  99. 99.
    Joyce JA, Fearon DT. 2015. T cell exclusion, immune privilege, and the tumor microenvironment. Science 348:74–80
     [Google Scholar]
  100. 100.
    Kagan VE, Mao G, Qu F, Angeli JP, Doll S et al. 2017. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol. 13:81–90
     [Google Scholar]
  101. 101.
    Kahn-Kirby AH, Amagata A, Maeder CI, Mei JJ, Sideris S et al. 2019. Targeting ferroptosis: a novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy. PLOS ONE 14:e0214250
     [Google Scholar]
  102. 102.
    Kapralov AA, Yang Q, Dar HH, Tyurina YY, Anthonymuthu TS et al. 2020. Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death. Nat. Chem. Biol. 16:278–90
     [Google Scholar]
  103. 103.
    Kathman SG, Boshart J, Jing H, Cravatt BF. 2020. Blockade of the lysophosphatidylserine lipase ABHD12 potentiates ferroptosis in cancer cells. ACS Chem. Biol. 15:871–77
     [Google Scholar]
  104. 104.
    Kim SE, Zhang L, Ma K, Riegman M, Chen F et al. 2016. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nat. Nanotechnol. 11:977–85
     [Google Scholar]
  105. 105.
    Kimura Y, Dargusch R, Schubert D, Kimura H. 2006. Hydrogen sulfide protects HT22 neuronal cells from oxidative stress. Antioxid. Redox. Signal. 8:661–70
     [Google Scholar]
  106. 106.
    Kobayashi S, Homma T, Okumura N, Han J, Nagaoka K et al. 2021. Carnosine dipeptidase II (CNDP2) protects cells under cysteine insufficiency by hydrolyzing glutathione-related peptides. Free Radic. Biol. Med. 174:12–27
     [Google Scholar]
  107. 107.
    Kraft VAN, Bezjian CT, Pfeiffer S, Ringelstetter L, Muller C et al. 2020. GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling. ACS Cent. Sci. 6:41–53
     [Google Scholar]
  108. 108.
    Kremer DM, Nelson BS, Lin L, Yarosz EL, Halbrook CJ et al. 2021. GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis. Nat. Commun. 12:4860
     [Google Scholar]
  109. 109.
    Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O et al. 2003. Characterization of mammalian selenoproteomes. Science 300:1439–43
     [Google Scholar]
  110. 110.
    Kwon MY, Park E, Lee SJ, Chung SW. 2015. Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death. Oncotarget 6:24393–403
     [Google Scholar]
  111. 111.
    La Rosa P, Petrillo S, Fiorenza MT, Bertini ES, Piemonte F 2020. Ferroptosis in Friedreich's ataxia: a metal-induced neurodegenerative disease. Biomolecules 10:1551
     [Google Scholar]
  112. 112.
    Lachaier E, Louandre C, Godin C, Saidak Z, Baert M et al. 2014. Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors. Anticancer Res. 34:6417–22
     [Google Scholar]
  113. 113.
    Larraufie MH, Yang WS, Jiang E, Thomas AG, Slusher BS, Stockwell BR. 2015. Incorporation of metabolically stable ketones into a small molecule probe to increase potency and water solubility. Bioorg. Med. Chem. Lett. 25:4787–92
     [Google Scholar]
  114. 114.
    Lautenschlager I, Pless-Petig G, Middel P, de Groot H, Rauen U, Stojanovic T. 2018. Cold storage injury to rat small-bowel transplants—beneficial effect of a modified HTK solution. Transplantation 102:1666–73
     [Google Scholar]
  115. 115.
    Lee H, Zandkarimi F, Zhang Y, Meena JK, Kim J et al. 2020. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat. Cell Biol. 22:225–34
     [Google Scholar]
  116. 116.
    Lei G, Zhang Y, Koppula P, Liu X, Zhang J et al. 2020. The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression. Cell Res. 30:146–62
     [Google Scholar]
  117. 117.
    Lei G, Zhuang L, Gan B. 2021. mTORC1 and ferroptosis: regulatory mechanisms and therapeutic potential. Bioessays 43:e2100093
     [Google Scholar]
  118. 118.
    Li C, Dong X, Du W, Shi X, Chen K et al. 2020. LKB1-AMPK axis negatively regulates ferroptosis by inhibiting fatty acid synthesis. Signal Transduct. Target. Ther. 5:187
     [Google Scholar]
  119. 119.
    Li W, Feng G, Gauthier JM, Lokshina I, Higashikubo R et al. 2019. Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation. J. Clin. Investig. 129:2293–304
     [Google Scholar]
  120. 120.
    Li X, Duan L, Yuan S, Zhuang X, Qiao T, He J. 2019. Ferroptosis inhibitor alleviates radiation-induced lung fibrosis (RILF) via down-regulation of TGF-β1. J. Inflamm. 16:11
     [Google Scholar]
  121. 121.
    Li Y, Feng D, Wang Z, Zhao Y, Sun R et al. 2019. Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion. Cell Death Differ. 26:2284–99
     [Google Scholar]
  122. 122.
    Li Y, Maher P, Schubert D. 1997. A role for 12-lipoxygenase in nerve cell death caused by glutathione depletion. Neuron 19:453–63
     [Google Scholar]
  123. 123.
    Liang C, Zhang X, Yang M, Dong X 2019. Recent progress in ferroptosis inducers for cancer therapy. Adv. Mater. 31:e1904197
     [Google Scholar]
  124. 124.
    Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C et al. 2014. Synchronized renal tubular cell death involves ferroptosis. PNAS 111:16836–41
     [Google Scholar]
  125. 125.
    Liu X, Olszewski K, Zhang Y, Lim EW, Shi J et al. 2020. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat. Cell Biol. 22:476–86
     [Google Scholar]
  126. 126.
    Liu X, Zhang Y, Zhuang L, Olszewski K, Gan B. 2021. NADPH debt drives redox bankruptcy: SLC7A11/xCT-mediated cystine uptake as a double-edged sword in cellular redox regulation. Genes Dis. 8:731–45
     [Google Scholar]
  127. 127.
    Liu Y, Wang Y, Liu J, Kang R, Tang D. 2021. Interplay between MTOR and GPX4 signaling modulates autophagy-dependent ferroptotic cancer cell death. Cancer Gene Ther. 28:55–63
     [Google Scholar]
  128. 128.
    Lorincz T, Jemnitz K, Kardon T, Mandl J, Szarka A. 2015. Ferroptosis is involved in acetaminophen induced cell death. Pathol. Oncol. Res. 21:1115–21
     [Google Scholar]
  129. 129.
    Lu SC. 2013. Glutathione synthesis. Biochim. Biophys. Acta Gen. Subj. 1830:3143–53
     [Google Scholar]
  130. 130.
    Ma X, Xiao L, Liu L, Ye L, Su P et al. 2021. CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability. Cell Metab. 33:1001–12.e5
     [Google Scholar]
  131. 131.
    MacDonald JI, Sprecher H. 1991. Phospholipid fatty acid remodeling in mammalian cells. Biochim. Biophys. Acta Lipids Lipid Metab. 1084:105–21
     [Google Scholar]
  132. 132.
    Magtanong L, Ko PJ, To M, Cao JY, Forcina GC et al. 2019. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem. Biol. 26:420–32.e9
     [Google Scholar]
  133. 133.
    Maiorino M, Conrad M, Ursini F 2018. GPx4, lipid peroxidation, and cell death: discoveries, rediscoveries, and open issues. Antioxid. Redox. Signal. 29:61–74
     [Google Scholar]
  134. 134.
    Mandal PK, Seiler A, Perisic T, Kolle P, Banjac Canak A et al. 2010. System xc− and thioredoxin reductase 1 cooperatively rescue glutathione deficiency. J. Biol. Chem. 285:22244–53
     [Google Scholar]
  135. 135.
    Mao C, Liu X, Zhang Y, Lei G, Yan Y et al. 2021. DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature 593:586–90
     [Google Scholar]
  136. 136.
    Masaldan S, Bush AI, Devos D, Rolland AS, Moreau C. 2019. Striking while the iron is hot: iron metabolism and ferroptosis in neurodegeneration. Free Radic. Biol. Med. 133:221–33
     [Google Scholar]
  137. 137.
    Matsushita M, Freigang S, Schneider C, Conrad M, Bornkamm GW, Kopf M. 2015. T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J. Exp. Med. 212:555–68
     [Google Scholar]
  138. 138.
    May JM, Morrow JD, Burk RF. 2002. Thioredoxin reductase reduces lipid hydroperoxides and spares α-tocopherol. Biochem. Biophys. Res. Commun. 292:45–49
     [Google Scholar]
  139. 139.
    Mayr L, Grabherr F, Schwarzler J, Reitmeier I, Sommer F et al. 2020. Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease. Nat. Commun. 11:1775
     [Google Scholar]
  140. 140.
    Melo AM, Bandeiras TM, Teixeira M. 2004. New insights into type II NAD(P)H:quinone oxidoreductases. Microbiol. Mol. Biol. Rev. 68:603–16
     [Google Scholar]
  141. 141.
    Mishima E, Fukuda S, Mukawa C, Yuri A, Kanemitsu Y et al. 2017. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach. Kidney Int. 92:634–45
     [Google Scholar]
  142. 142.
    Mishima E, Sato E, Ito J, Yamada KI, Suzuki C et al. 2020. Drugs repurposed as antiferroptosis agents suppress organ damage, including AKI, by functioning as lipid peroxyl radical scavengers. J. Am. Soc. Nephrol. 31:280–96
     [Google Scholar]
  143. 143.
    Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T et al. 2012. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 22:66–79
     [Google Scholar]
  144. 144.
    Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A et al. 2020. Selenium deficiency is associated with mortality risk from COVID-19. Nutrients 12:2098
     [Google Scholar]
  145. 145.
    Moreno-Garcia A, Kun A, Calero O, Medina M, Calero M. 2018. An overview of the role of lipofuscin in age-related neurodegeneration. Front. Neurosci. 12:464
     [Google Scholar]
  146. 146.
    Mumbauer S, Pascual J, Kolotuev I, Hamaratoglu F. 2019. Ferritin heavy chain protects the developing wing from reactive oxygen species and ferroptosis. PLOS Genet. 15:e1008396
     [Google Scholar]
  147. 147.
    Nakamura T, Ogawa M, Kojima K, Takayanagi S, Ishihara S et al. 2021. The mitochondrial Ca2+ uptake regulator, MICU1, is involved in cold stress-induced ferroptosis. EMBO Rep. 22:e51532
     [Google Scholar]
  148. 148.
    Nguyen HP, Yi D, Lin F, Viscarra JA, Tabuchi C et al. 2020. Aifm2, a NADH oxidase, supports robust glycolysis and is required for cold- and diet-induced thermogenesis. Mol. Cell 77:600–17.e4
     [Google Scholar]
  149. 149.
    Nishizawa H, Matsumoto M, Shindo T, Saigusa D, Kato H et al. 2020. Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1. J. Biol. Chem. 295:69–82
     [Google Scholar]
  150. 150.
    Olm E, Fernandes AP, Hebert C, Rundlof AK, Larsen EH et al. 2009. Extracellular thiol-assisted selenium uptake dependent on the xc− cystine transporter explains the cancer-specific cytotoxicity of selenite. PNAS 106:11400–5
     [Google Scholar]
  151. 151.
    Ooko E, Saeed ME, Kadioglu O, Sarvi S, Colak M et al. 2015. Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells. Phytomedicine 22:1045–54
     [Google Scholar]
  152. 152.
    Paton CM, Ntambi JM. 2009. Biochemical and physiological function of stearoyl-CoA desaturase. Am. J. Physiol. Endocrinol. Metab. 297:E28–37
     [Google Scholar]
  153. 153.
    Perez MA, Magtanong L, Dixon SJ, Watts JL. 2020. Dietary lipids induce ferroptosis in Caenorhabditis elegans and human cancer cells. Dev. Cell 54:447–54.e4
     [Google Scholar]
  154. 154.
    Porter NA, Caldwell SE, Mills KA. 1995. Mechanisms of free radical oxidation of unsaturated lipids. Lipids 30:277–90
     [Google Scholar]
  155. 155.
    Protchenko O, Baratz E, Jadhav S, Li F, Shakoury-Elizeh M et al. 2021. Iron chaperone poly rC binding protein 1 protects mouse liver from lipid peroxidation and steatosis. Hepatology 73:1176–93
     [Google Scholar]
  156. 156.
    Qian X, Zhang J, Gu Z, Chen Y. 2019. Nanocatalysts-augmented Fenton chemical reaction for nanocatalytic tumor therapy. Biomaterials 211:1–13
     [Google Scholar]
  157. 157.
    Rahmania H, Kato S, Sawada K, Hayashi C, Hashimoto H et al. 2020. Revealing the thermal oxidation stability and its mechanism of rice bran oil. Sci. Rep. 10:14091
     [Google Scholar]
  158. 158.
    Ramasamy T, Sundaramoorthy P, Ruttala HB, Choi Y, Shin WH et al. 2017. Polyunsaturated fatty acid-based targeted nanotherapeutics to enhance the therapeutic efficacy of docetaxel. Drug Deliv. 24:1262–72
     [Google Scholar]
  159. 159.
    Sato H, Fujiwara K, Sagara J, Bannai S. 1995. Induction of cystine transport activity in mouse peritoneal macrophages by bacterial lipopolysaccharide. Biochem. J. 310:Part 2547–51
     [Google Scholar]
  160. 160.
    Sato H, Tamba M, Ishii T, Bannai S. 1999. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J. Biol. Chem. 274:11455–58
     [Google Scholar]
  161. 161.
    Sato M, Kusumi R, Hamashima S, Kobayashi S, Sasaki S et al. 2018. The ferroptosis inducer erastin irreversibly inhibits system xc− and synergizes with cisplatin to increase cisplatin's cytotoxicity in cancer cells. Sci. Rep. 8:968
     [Google Scholar]
  162. 162.
    Sato M, Onuma K, Domon M, Hasegawa S, Suzuki A et al. 2020. Loss of the cystine/glutamate antiporter in melanoma abrogates tumor metastasis and markedly increases survival rates of mice. Int. J. Cancer 147:3224–35
     [Google Scholar]
  163. 163.
    Schwarz K, Foltz CM. 1958. Factor 3 activity of selenium compounds. J. Biol. Chem. 233:245–51
     [Google Scholar]
  164. 164.
    Seiler A, Schneider M, Forster H, Roth S, Wirth EK et al. 2008. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab. 8:237–48
     [Google Scholar]
  165. 165.
    Shah R, Shchepinov MS, Pratt DA. 2018. Resolving the role of lipoxygenases in the initiation and execution of ferroptosis. ACS Cent. Sci. 4:387–96
     [Google Scholar]
  166. 166.
    Shang Y, Luo M, Yao F, Wang S, Yuan Z, Yang Y. 2020. Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cell. Signal. 72:109633
     [Google Scholar]
  167. 167.
    Sharma S, Leaf DE. 2019. Iron chelation as a potential therapeutic strategy for AKI prevention. J. Am. Soc. Nephrol. 30:2060–71
     [Google Scholar]
  168. 168.
    Shchepinov MS. 2020. Polyunsaturated fatty acid deuteration against neurodegeneration. Trends Pharmacol. Sci. 41:236–48
     [Google Scholar]
  169. 169.
    Shen Q, Liang M, Yang F, Deng YZ, Naqvi NI. 2020. Ferroptosis contributes to developmental cell death in rice blast. New Phytol. 227:1831–46
     [Google Scholar]
  170. 170.
    Shimada K, Hayano M, Pagano NC, Stockwell BR. 2016. Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity. Cell Chem. Biol. 23:225–35
     [Google Scholar]
  171. 171.
    Shimada K, Skouta R, Kaplan A, Yang WS, Hayano M et al. 2016. Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat. Chem. Biol. 12:497–503
     [Google Scholar]
  172. 172.
    Smith AC, Mears AJ, Bunker R, Ahmed A, MacKenzie M et al. 2014. Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia. J. Med. Genet. 51:470–74
     [Google Scholar]
  173. 173.
    Song X, Liu J, Kuang F, Chen X, Zeh HJ 3rd et al. 2021. PDK4 dictates metabolic resistance to ferroptosis by suppressing pyruvate oxidation and fatty acid synthesis. Cell Rep. 34:108767
     [Google Scholar]
  174. 174.
    Song Y, Wang B, Zhu X, Hu J, Sun J 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
     [Google Scholar]
  175. 175.
    Sonowal R, Swimm A, Sahoo A, Luo L, Matsunaga Y et al. 2017. Indoles from commensal bacteria extend healthspan. PNAS 114:E7506–15
     [Google Scholar]
  176. 176.
    Soula M, Weber RA, Zilka O, Alwaseem H, La K et al. 2020. Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers. Nat. Chem. Biol. 16:1351–60
     [Google Scholar]
  177. 177.
    Southon A, Szostak K, Acevedo KM, Dent KA, Volitakis I et al. 2020. CuII (atsm) inhibits ferroptosis: implications for treatment of neurodegenerative disease. Br. J. Pharmacol. 177:656–67
     [Google Scholar]
  178. 178.
    Steinbrenner H, Al-Quraishy S, Dkhil MA, Wunderlich F, Sies H. 2015. Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv. Nutr. 6:73–82
     [Google Scholar]
  179. 179.
    Sun WY, Tyurin VA, Mikulska-Ruminska K, Shrivastava IH, Anthonymuthu TS et al. 2021. Phospholipase iPLA2β averts ferroptosis by eliminating a redox lipid death signal. Nat. Chem. Biol. 17:465–76
     [Google Scholar]
  180. 180.
    Sun X, Ou Z, Chen R, Niu X, Chen D et al. 2016. Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology 63:173–84
     [Google Scholar]
  181. 181.
    Suzuki Y, Nakagawa K, Kato S, Tatewaki N, Mizuochi S et al. 2015. Metabolism and cytotoxic effects of phosphatidylcholine hydroperoxide in human hepatoma HepG2 cells. Biochem. Biophys. Res. Commun. 458:920–27
     [Google Scholar]
  182. 182.
    Tadokoro T, Ikeda M, Ide T, Deguchi H, Ikeda S et al. 2020. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight 5:e132747
     [Google Scholar]
  183. 183.
    Tan S, Schubert D, Maher P. 2001. Oxytosis: a novel form of programmed cell death. Curr. Top. Med. Chem. 1:497–506
     [Google Scholar]
  184. 184.
    Tesfay L, Paul BT, Konstorum A, Deng Z, Cox AO et al. 2019. Stearoyl-CoA desaturase 1 protects ovarian cancer cells from ferroptotic cell death. Cancer Res. 79:5355–66
     [Google Scholar]
  185. 185.
    Thomas JP, Maiorino M, Ursini F, Girotti AW. 1990. Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. J. Biol. Chem. 265:454–61
     [Google Scholar]
  186. 186.
    Tian R, Abarientos A, Hong J, Hashemi SH, Yan R et al. 2021. Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis. Nat. Neurosci. 24:1020–34
     [Google Scholar]
  187. 187.
    Tonnus W, Meyer C, Steinebach C, Belavgeni A, von Massenhausen A et al. 2021. Dysfunction of the key ferroptosis-surveilling systems hypersensitizes mice to tubular necrosis during acute kidney injury. Nat. Commun. 12:4402
     [Google Scholar]
  188. 188.
    Tsoi J, Robert L, Paraiso K, Galvan C, Sheu KM et al. 2018. Multi-stage differentiation defines melanoma subtypes with differential vulnerability to drug-induced iron-dependent oxidative stress. Cancer Cell 33:890–904.e5
     [Google Scholar]
  189. 189.
    Tu Y. 2011. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat. Med. 17:1217–20
     [Google Scholar]
  190. 190.
    Tuo QZ, Lei P, Jackman KA, Li XL, Xiong H et al. 2017. Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. Mol. Psychiatry 22:1520–30
     [Google Scholar]
  191. 191.
    Ubellacker JM, Tasdogan A, Ramesh V, Shen B, Mitchell EC et al. 2020. Lymph protects metastasizing melanoma cells from ferroptosis. Nature 585:113–18
     [Google Scholar]
  192. 192.
    Ueta T, Inoue T, Furukawa T, Tamaki Y, Nakagawa Y et al. 2012. Glutathione peroxidase 4 is required for maturation of photoreceptor cells. J. Biol. Chem. 287:7675–82
     [Google Scholar]
  193. 193.
    Ulatowski LM, Manor D. 2015. Vitamin E and neurodegeneration. Neurobiol. Dis. 84:78–83
     [Google Scholar]
  194. 194.
    Ursini F, Bindoli A. 1987. The role of selenium peroxidases in the protection against oxidative damage of membranes. Chem. Phys. Lipids. 44:255–76
     [Google Scholar]
  195. 195.
    Ursini F, Maiorino M, Gregolin C. 1985. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochim. Biophys. Acta Gen. Subj. 839:62–70
     [Google Scholar]
  196. 196.
    Viswanathan VS, Ryan MJ, Dhruv HD, Gill S, Eichhoff OM et al. 2017. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547:453–57
     [Google Scholar]
  197. 197.
    Vriens K, Christen S, Parik S, Broekaert D, Yoshinaga K et al. 2019. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity. Nature 566:403–6
     [Google Scholar]
  198. 198.
    Vuckovic AM, Venerando R, Tibaldi E, Bosello Travain V, Roveri A et al. 2021. Aerobic pyruvate metabolism sensitizes cells to ferroptosis primed by GSH depletion. Free Radic. Biol. Med. 167:45–53
     [Google Scholar]
  199. 199.
    Wang H, An P, Xie E, Wu Q, Fang X et al. 2017. Characterization of ferroptosis in murine models of hemochromatosis. Hepatology 66:449–65
     [Google Scholar]
  200. 200.
    Wang S, Luo J, Zhang Z, Dong D, Shen Y et al. 2018. Iron and magnetic: new research direction of the ferroptosis-based cancer therapy. Am. J. Cancer Res. 8:1933–46
     [Google Scholar]
  201. 201.
    Wang W, Green M, Choi JE, Gijon M, Kennedy PD et al. 2019. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 569:270–74
     [Google Scholar]
  202. 202.
    Wang Y, Hekimi S. 2016. Understanding ubiquinone. Trends Cell Biol. 26:367–78
     [Google Scholar]
  203. 203.
    Wang Y, Huang J, Sun Y, Stubbs D, He J et al. 2021. SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, endoplasmic reticulum stress and DNA synthesis. Food Chem. Toxicol. 153:112286
     [Google Scholar]
  204. 204.
    Wang Y, Yu R, Wu L, Yang G 2021. Hydrogen sulfide guards myoblasts from ferroptosis by inhibiting ALOX12 acetylation. Cell. Signal. 78:109870
     [Google Scholar]
  205. 205.
    Weiwer M, Bittker JA, Lewis TA, Shimada K, Yang WS et al. 2012. Development of small-molecule probes that selectively kill cells induced to express mutant RAS. Bioorg. Med. Chem. Lett. 22:1822–26
     [Google Scholar]
  206. 206.
    Wenzel SE, Tyurina YY, Zhao J, St Croix CM, Dar HH et al. 2017. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell 171:628–41.e26
     [Google Scholar]
  207. 207.
    Wirth EK, Conrad M, Winterer J, Wozny C, Carlson BA et al. 2010. Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration. FASEB J. 24:844–52
     [Google Scholar]
  208. 208.
    Wolfson RL, Sabatini DM. 2017. The dawn of the age of amino acid sensors for the mTORC1 pathway. Cell Metab. 26:301–9
     [Google Scholar]
  209. 209.
    Wortmann M, Schneider M, Pircher J, Hellfritsch J, Aichler M et al. 2013. Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. Circ. Res. 113:408–17
     [Google Scholar]
  210. 210.
    Wu J, Minikes AM, Gao M, Bian H, Li Y et al. 2019. Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling. Nature 572:402–6
     [Google Scholar]
  211. 211.
    Xie S, Sun W, Zhang C, Dong B, Yang J et al. 2021. Metabolic control by heat stress determining cell fate to ferroptosis for effective cancer therapy. ACS Nano 15:7179–94
     [Google Scholar]
  212. 212.
    Xu H, Ye D, Ren M, Zhang H, Bi F. 2021. Ferroptosis in the tumor microenvironment: perspectives for immunotherapy. Trends Mol. Med. 27:856–67
     [Google Scholar]
  213. 213.
    Yamada N, Karasawa T, Wakiya T, Sadatomo A, Ito H et al. 2020. Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: potential role of ferroptosis. Am. J. Transplant. 20:1606–18
     [Google Scholar]
  214. 214.
    Yan B, Ai Y, Sun Q, Ma Y, Cao Y et al. 2021. Membrane damage during ferroptosis is caused by oxidation of phospholipids catalyzed by the oxidoreductases POR and CYB5R1. Mol. Cell 81:355–69.e10
     [Google Scholar]
  215. 215.
    Yang M, Lai CL. 2020. SARS-CoV-2 infection: Can ferroptosis be a potential treatment target for multiple organ involvement?. Cell Death Discov. 6:130
     [Google Scholar]
  216. 216.
    Yang WH, Ding CC, Sun T, Rupprecht G, Lin CC et al. 2019. The Hippo pathway effector TAZ regulates ferroptosis in renal cell carcinoma. Cell Rep. 28:2501–8.e4
     [Google Scholar]
  217. 217.
    Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. 2016. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. PNAS 113:E4966–75
     [Google Scholar]
  218. 218.
    Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R et al. 2014. Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317–31
     [Google Scholar]
  219. 219.
    Yant LJ, Ran Q, Rao L, Van Remmen H, Shibatani T et al. 2003. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic. Biol. Med. 34:496–502
     [Google Scholar]
  220. 220.
    Yao F, Cui X, Zhang Y, Bei Z, Wang H et al. 2021. Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma. Oncol. Lett. 22:657
     [Google Scholar]
  221. 221.
    Yao Y, Chen S, Li H 2021. An improved system to evaluate superoxide-scavenging effects of bioflavonoids. ChemistryOpen 10:503–14
     [Google Scholar]
  222. 222.
    Yi J, Zhu J, Wu J, Thompson CB, Jiang X. 2020. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. PNAS 117:31189–97
     [Google Scholar]
  223. 223.
    Zeitler L, Fiore A, Meyer C, Russier M, Zanella G et al. 2021. Anti-ferroptotic mechanism of IL4i1-mediated amino acid metabolism. Elife 10:e64806
     [Google Scholar]
  224. 224.
    Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP. 2020. Association between regional selenium status and reported outcome of COVID-19 cases in China. Am. J. Clin. Nutr. 111:1297–99
     [Google Scholar]
  225. 225.
    Zhang X, Xing X, Liu H, Feng J, Tian M et al. 2020. Ionizing radiation induces ferroptosis in granulocyte-macrophage hematopoietic progenitor cells of murine bone marrow. Int. J. Radiat. Biol. 96:584–95
     [Google Scholar]
  226. 226.
    Zhang Y, Swanda RV, Nie L, Liu X, Wang C et al. 2021. mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation. Nat. Commun. 12:1589
     [Google Scholar]
  227. 227.
    Zhang Y, Tan H, Daniels JD, Zandkarimi F, Liu H et al. 2019. Imidazole ketone erastin induces ferroptosis and slows tumor growth in a mouse lymphoma model. Cell Chem. Biol. 26:623–33.e9
     [Google Scholar]
  228. 228.
    Zheng J, Conrad M. 2020. The metabolic underpinnings of ferroptosis. Cell Metab. 32:6920–37
     [Google Scholar]
  229. 229.
    Zheng J, Sato M, Mishima E, Sato H, Proneth B, Conrad M. 2021. Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines. Cell Death. Dis. 12:698
     [Google Scholar]
  230. 230.
    Zilka O, Shah R, Li B, Friedmann Angeli JP, Griesser M et al. 2017. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent. Sci. 3:232–43
     [Google Scholar]
  231. 231.
    Zou Y, Henry WS, Ricq EL, Graham ET, Phadnis VV et al. 2020. Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Nature 585:603–8
     [Google Scholar]
  232. 232.
    Zou Y, Li H, Graham ET, Deik AA, Eaton JK et al. 2020. Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat. Chem. Biol. 16:302–9
     [Google Scholar]
  233. 233.
    Zou Y, Palte MJ, Deik AA, Li H, Eaton JK et al. 2019. A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat. Commun. 10:1617
     [Google Scholar]
/content/journals/10.1146/annurev-nutr-062320-114541
Loading
Nutritional and Metabolic Control of Ferroptosis
Annual Review of Nutrition 42, 275 (2022); https://doi.org/10.1146/annurev-nutr-062320-114541
/content/journals/10.1146/annurev-nutr-062320-114541
/content/journals/10.1146/annurev-nutr-062320-114541
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error