Ferroptosis caused by cysteine insufficiency and oxidative insult

References

• Tang D, Kang R, Berghe TV, et al. The molecular machinery of regulated cell death. Cell Res. 2019;29(5):347–364.
   PubMed Web of Science ®Google Scholar
• Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med. 2009;47(5):469–484.
   PubMed Web of Science ®Google Scholar
• Guéraud F, Atalay M, Bresgen N, et al. Chemistry and biochemistry of lipid peroxidation products. Free Radic Res. 2010;44(10):1098–1124.
   PubMed Web of Science ®Google Scholar
• Uchida K. HNE as an inducer of COX-2. Free Radic Biol Med. 2017;111:169–172.
   PubMed Web of Science ®Google Scholar
• Nagata S. Apoptosis and clearance of apoptotic cells. Annu Rev Immunol. 2018;36:489–517.
   PubMed Web of Science ®Google Scholar
• Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–1072.
   PubMed Web of Science ®Google Scholar
• Toyokuni S, Ito F, Yamashita K, et al. Iron and thiol redox signaling in cancer: an exquisite balance to escape ferroptosis. Free Radic Biol Med. 2017;108:610–626.
   PubMed Web of Science ®Google Scholar
• Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273–285.
   PubMed Web of Science ®Google Scholar
• Hirschhorn T, Stockwell BR. The development of the concept of ferroptosis. Fee Radic Biol Med. 2019;133:130–143.
   PubMed Web of Science ®Google Scholar
• Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156(1–2):317–331.
   PubMed Web of Science ®Google Scholar
• Friedmann Angeli JP, Schneider M, Proneth B, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014;16(12):1180–1191.
   PubMed Web of Science ®Google Scholar
• Sato H, Tamba M, Ishii T, et al. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem. 1999;274(17):11455–11458.
   PubMed Web of Science ®Google Scholar
• Kang R, Kroemer G, Tang D. The tumor suppressor protein p53 and the ferroptosis network. Free Radic Biol Med. 2019;133:162–168.
   PubMed Web of Science ®Google Scholar
• Suto D, Sato K, Ohba Y, et al. Suppression of the pro-apoptotic function of cytochrome c by singlet oxygen via a haem redox state-independent mechanism. Biochem J. 2005;392(2):399–406.
   PubMedGoogle Scholar
• Hansen JM, Go YM, Jones DP. Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Annu Rev Pharmacol Toxicol. 2006;46:215–234.
   PubMed Web of Science ®Google Scholar
• Feng H, Stockwell BR. Unsolved mysteries: how does lipid peroxidation cause ferroptosis? PLOS Biol. 2018;16(5):e2006203.
   PubMed Web of Science ®Google Scholar
• Tang M, Chen Z, Wu D, et al. Ferritinophagy/ferroptosis: iron-related newcomers in human diseases. J Cell Physiol. 2018;233(12):9179–9190.
   PubMed Web of Science ®Google Scholar
• Latunde-Dada GO. Ferroptosis: role of lipid peroxidation, iron and ferritinophagy. Biochim Biophys Acta. 2017;1861(8):1893–1900.
   PubMed Web of Science ®Google Scholar
• Skouta R, Dixon SJ, Wang J, et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc. 2014;136(12):4551–4556.
   PubMed Web of Science ®Google Scholar
• Zilka O, Shah R, Li B, et al. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent Sci. 2017;3(3):232–243.
   PubMed Web of Science ®Google Scholar
• Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell. 2018;172(3):409–422.e21.
   PubMed Web of Science ®Google Scholar
• Yuan H, Li X, Zhang X, et al. Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun. 2016;478(3):1338–1343.
   PubMed Web of Science ®Google Scholar
• Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2017;13(1):91–98.
   PubMed Web of Science ®Google Scholar
• Doll S, Conrad M. Iron and ferroptosis: a still ill-defined liaison. IUBMB Life. 2017;69(6):423–434.
   PubMed Web of Science ®Google Scholar
• Krainz T, Gaschler MM, Lim C, et al. A mitochondrial-targeted nitroxide is a potent inhibitor of ferroptosis. ACS Cent Sci. 2016;2(9):653–659.
   PubMed Web of Science ®Google Scholar
• Schöneich C. Thiyl radicals and induction of protein degradation. Free Radic Res. 2016;50(2):143–149.
   PubMed Web of Science ®Google Scholar
• Gao M, Yi J, Zhu J, et al. Role of mitochondria in ferroptosis. Mol Cell. 2019;73(2):354–363.e3.
   PubMed Web of Science ®Google Scholar
• Shah R, Margison K, Pratt DA. The potency of diarylamine radical-trapping antioxidants as inhibitors of ferroptosis underscores the role of autoxidation in the mechanism of cell death. ACS Chem Biol. 2017;12(10):2538–2545.
   PubMed Web of Science ®Google Scholar
• Homma T, Kobayashi S, Fujii J. Induction of ferroptosis by singlet oxygen generated from naphthalene endoperoxide. Biochem Biophys Res Commun. 2019;518:519–525.
   PubMed Web of Science ®Google Scholar
• Klotz LO, Holbrook NJ, Sies H. UVA and singlet oxygen as inducers of cutaneous signaling events. Curr Probl Dermatol. 2001;29:95–113.
   PubMedGoogle Scholar
• Chilakamarthi U, Giribabu L. Photodynamic therapy: past, present and future. Chem Rec. 2017;17(8):775–802.
   PubMed Web of Science ®Google Scholar
• Kaur J, Debnath J. Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol. 2015;16(8):461–472.
   PubMed Web of Science ®Google Scholar
• Torii S, Shintoku R, Kubota C, et al. An essential role for functional lysosomes in ferroptosis of cancer cells. Biochem J. 2016;473(6):769–777.
   PubMedGoogle Scholar
• Hou W, Xie Y, Song X, et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 2016;12(8):1425–1428.
   PubMed Web of Science ®Google Scholar
• Gao M, Monian P, Quadri N, et al. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell. 2015;59(2):298–308.
   PubMed Web of Science ®Google Scholar
• Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol. 2010;50:323–354.
   PubMed Web of Science ®Google Scholar
• Adedoyin O, Boddu R, Traylor A, et al. Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells. Am J Physiol Renal Physiol. 2018;314(5):F702–F714.
   PubMed Web of Science ®Google Scholar
• Kwon MY, Park E, Lee SJ, et al. Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death. Oncotarget. 2015;6(27):24393–24403.
   PubMedGoogle Scholar
• Chiang SK, Chen SE, Chang LC. A dual role of heme oxygenase-1 in cancer cells. Int J Mol Sci. 2018;20(1):E39.
   PubMed Web of Science ®Google Scholar
• Karmi O, Marjault HB, Pesce L, et al. The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease. J Biol Inorg Chem. 2018;23(4):599–612.
   PubMed Web of Science ®Google Scholar
• Karmi O, Holt SH, Song L, et al. Interactions between mitoNEET and NAF-1 in cells. PLoS One. 2017;12(4):e0175796.
   PubMed Web of Science ®Google Scholar
• Yuan H, Li X, Zhang X, et al. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem Biophys Res Commun. 2016;478(2):838–844.
   PubMed Web of Science ®Google Scholar
• Kim EH, Shin D, Lee J, et al. CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer. Cancer Lett. 2018;432:180–190.
   PubMed Web of Science ®Google Scholar
• Lill R, Dutkiewicz R, Freibert SA, et al. The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron–sulfur proteins. Eur J Cell Biol. 2015;94(7–9):280–291.
   PubMed Web of Science ®Google Scholar
• Alvarez SW, Sviderskiy VO, Terzi EM, et al. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature. 2017;551(7682):639–643.
   PubMed Web of Science ®Google Scholar
• Du J, Wang T, Li Y, et al. XDHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin. Free Radic Biol Med. 2019;131:356–369.
   PubMed Web of Science ®Google Scholar
• Imai H. New strategy of functional analysis of PHGPx knockout mice model using transgenic rescue method and Cre–LoxP system. J Clin Biochem Nutr. 2010;46(1):1–13.
   PubMed Web of Science ®Google Scholar
• Rhee SG, Kil IS. Multiple functions and regulation of mammalian peroxiredoxins. Annu Rev Biochem. 2017;86:749–775.
   PubMed Web of Science ®Google Scholar
• Viswanathan VS, Ryan MJ, Dhruv HD, et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature. 2017;547(7664):453–457.
   PubMed Web of Science ®Google Scholar
• Seibt TM, Proneth B, Conrad M. Role of GPX4 in ferroptosis and its pharmacological implication. Free Radic Biol Med. 2019;133:144–152.
   PubMed Web of Science ®Google Scholar
• Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008;15(3):234–245.
   PubMedGoogle Scholar
• Gaschler MM, Andia AA, Liu H, et al. FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat Chem Biol. 2018;14(5):507–515.
   PubMed Web of Science ®Google Scholar
• Hassannia B, Wiernicki B, Ingold I, et al. Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. J Clin Invest. 2018;128(8):3341–3355.
   PubMed Web of Science ®Google Scholar
• Conrad M, Sato H. The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (–): cystine supplier and beyond. Amino Acids. 2012;42(1):231–246.
   PubMed Web of Science ®Google Scholar
• McBean GJ. The transsulfuration pathway: a source of cysteine for glutathione in astrocytes. Amino Acids. 2012;42(1):199–205.
   PubMed Web of Science ®Google Scholar
• Kang ES, Lee J, Homma T, et al. xCT deficiency aggravates acetaminophen-induced hepatotoxicity under inhibition of the transsulfuration pathway. Free Radic Res. 2017;51(1):80–90.
   PubMed Web of Science ®Google Scholar
• Hayano M, Yang WS, Corn CK, et al. Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ. 2016;23(2):270–278.
   PubMed Web of Science ®Google Scholar
• Cramer SL, Saha A, Liu J, et al. Systemic depletion of l-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth. Nat Med. 2017;23(1):120–127.
   PubMed Web of Science ®Google Scholar
• Ruivo R, Bellenchi GC, Chen X, et al. Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin. Proc Natl Acad Sci USA. 2012;109(5):E210–E217.
   PubMed Web of Science ®Google Scholar
• Ishimoto T, Nagano O, Yae T, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(–) and thereby promotes tumor growth. Cancer Cell. 2011;19(3):387–400.
   PubMed Web of Science ®Google Scholar
• Sato H, Tamba M, Kuriyama-Matsumura K, et al. Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc−. Antioxid Redox Signal. 2000;2(4):665–671.
   PubMed Web of Science ®Google Scholar
• Kobayashi S, Sato M, Kasakoshi T, et al. Cystathionine is a novel substrate of cystine/glutamate transporter: implications for immune function. J Biol Chem. 2015;290(14):8778–8788.
   PubMed Web of Science ®Google Scholar
• Shibasaki T, Iuchi Y, Okada F, et al. Aggravation of ischemia-reperfusion-triggered acute renal failure in xCT-deficient mice. Arch Biochem Biophys. 2009;490(1):63–69.
   PubMed Web of Science ®Google Scholar
• Kobayashi S, Kuwata K, Sugimoto T, et al. Enhanced expression of cystine/glutamate transporter in the lung caused by the oxidative-stress-inducing agent paraquat. Free Radic Biol Med. 2012;53(12):2197–2203.
   PubMed Web of Science ®Google Scholar
• Lee J, Kang ES, Kobayashi S, et al. The viability of primary hepatocytes is maintained under a low cysteine-glutathione redox state with a marked elevation in ophthalmic acid production. Exp Cell Res. 2017;361(1):178–191.
   PubMed Web of Science ®Google Scholar
• Ishii T, Mann GE. Redox status in mammalian cells and stem cells during culture in vitro: critical roles of Nrf2 and cystine transporter activity in the maintenance of redox balance. Redox Biol. 2014;2:786–794.
   PubMed Web of Science ®Google Scholar
• Sato M, Kusumi R, Hamashima S, et al. The ferroptosis inducer erastin irreversibly inhibits system xc- and synergizes with cisplatin to increase cisplatin’s cytotoxicity in cancer cells. Sci Rep. 2018;8(1):968.
   PubMed Web of Science ®Google Scholar
• Bridges RJ, Natale NR, Patel SA. System xc– cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. Br J Pharmacol. 2012;165(1):20–34.
   PubMed Web of Science ®Google Scholar
• Sato H, Shiiya A, Kimata M, et al. Redox imbalance in cystine/glutamate transporter-deficient mice. J Biol Chem. 2005;280(45):37423–37429.
   PubMed Web of Science ®Google Scholar
• Massie A, Boillée S, Hewett S, et al. Main path and byways: non-vesicular glutamate release by system xc(–) as an important modifier of glutamatergic neurotransmission. J Neurochem. 2015;135(6):1062–1079.
   PubMed Web of Science ®Google Scholar
• Kobayashi S, Hamashima S, Homma T, et al. Cystine/glutamate transporter, system xc−, is involved in nitric oxide production in mouse peritoneal macrophages. Nitric Oxide. 2018;78:32–40.
   PubMed Web of Science ®Google Scholar
• Song X, Zhu S, Chen P, et al. AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc− activity. Curr Biol. 2018;28(15):2388–2399.e5.
   PubMed Web of Science ®Google Scholar
• Fujii J, Ito JI, Zhang X, et al. Unveiling the roles of the glutathione redox system in vivo by analyzing genetically modified mice. J Clin Biochem Nutr. 2011;49(2):70–78.
   PubMed Web of Science ®Google Scholar
• Meister A, Anderson ME. Glutathione. Annu Rev Biochem. 1983;52:711–760.
   PubMed Web of Science ®Google Scholar
• Griffith OW. Biologic and pharmacologic regulation of mammalian glutathione synthesis. Free Radic Biol Med. 1999;27(9–10):922–935.
   PubMed Web of Science ®Google Scholar
• Soga T, Baran R, Suematsu M, et al. Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. J Biol Chem. 2006;281(24):16768–16776.
   PubMed Web of Science ®Google Scholar
• Kobayashi S, Lee J, Takao T, et al. Increased ophthalmic acid production is supported by amino acid catabolism under fasting conditions in mice. Biochem Biophys Res Commun. 2017;491(3):649–655.
   PubMed Web of Science ®Google Scholar
• Zarka MH, Bridge WJ. Oral administration of γ-glutamylcysteine increases intracellular glutathione levels above homeostasis in a randomised human trial pilot study. Redox Biol. 2017;11:631–636.
   PubMed Web of Science ®Google Scholar
• Ikeda Y, Taniguchi N. Gene expression of gamma-glutamyltranspeptidase. Methods Enzymol. 2005;401:408–425.
   PubMed Web of Science ®Google Scholar
• Newstead S. Molecular insights into proton coupled peptide transport in the PTR family of oligopeptide transporters. Biochim Biophys Acta. 2015;1850(3):488–499.
   PubMed Web of Science ®Google Scholar
• Kandasamy P, Gyimesi G, Kanai Y, et al. Amino acid transporters revisited: new views in health and disease. Trends Biochem Sci. 2018;43(10):752–789.
   PubMed Web of Science ®Google Scholar
• Dringen R, Pfeiffer B, Hamprecht B. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J Neurosci. 1999;19(2):562–569.
   PubMed Web of Science ®Google Scholar
• Yamamoto M, Kensler TW, Motohashi H. The KEAP1–NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol Rev. 2018;98(3):1169–1203.
   PubMed Web of Science ®Google Scholar
• Ishii T, Itoh K, Takahashi S, et al. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem. 2000;275(21):16023–16029.
   PubMed Web of Science ®Google Scholar
• Sun X, Ou Z, Chen R, et al. Activation of the p62–Keap1–NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology. 2016;63(1):173–184.
   PubMed Web of Science ®Google Scholar
• Roh JL, Kim EH, Jang H, et al. Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol. 2017;11:254–262.
   PubMed Web of Science ®Google Scholar
• Sato H, Nomura S, Maebara K, et al. Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation. Biochem Biophys Res Commun. 2004;325(1):109–116.
   PubMed Web of Science ®Google Scholar
• Ye P, Mimura J, Okada T, et al. Nrf2- and ATF4-dependent upregulation of xCT modulates the sensitivity of T24 bladder carcinoma cells to proteasome inhibition. Mol Cell Biol. 2014;34(18):3421–3434.
   PubMed Web of Science ®Google Scholar
• Chen D, Fan Z, Rauh M, et al. ATF4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xCT-dependent manner. Oncogene. 2017;36(40):5593–5608.
   PubMed Web of Science ®Google Scholar
• Chen D, Rauh M, Buchfelder M, et al. The oxido-metabolic driver ATF4 enhances temozolamide chemo-resistance in human gliomas. Oncotarget. 2017;8(31):51164–51176.
   PubMedGoogle Scholar
• Kang R, Tang D. Autophagy and ferroptosis – what’s the connection? Curr Pathobiol Rep. 2017;5(2):153–159.
   PubMedGoogle Scholar
• Tarangelo A, Magtanong L, Bieging-Rolett KT, et al. p53 suppresses metabolic stress-induced ferroptosis in cancer cells. Cell Rep. 2018;22(3):569–575.
   PubMed Web of Science ®Google Scholar
• Friedmann Angeli JP, Krysko DV, Conrad M. Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer. 2019;19(7):405–414.
   PubMed Web of Science ®Google Scholar
• Jiang L, Kon N, Li T, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 2015;520(7545):57–62.
   PubMed Web of Science ®Google Scholar
• Chu B, Kon N, Chen D, et al. ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway. Nat Cell Biol. 2019;21(5):579–591.
   PubMed Web of Science ®Google Scholar
• Wang Y, Yang L, Zhang X, et al. Epigenetic regulation of ferroptosis by H2B monoubiquitination and p53. EMBO Rep. 2019;20(7):e47563.
   PubMed Web of Science ®Google Scholar
• Xie Y, Zhu S, Song X, et al. The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity. Cell Rep. 2017;20(7):1692–1704.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Shi J, Liu X, et al. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol. 2018;20(10):1181–1192.
   PubMed Web of Science ®Google Scholar