Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation

Cell Death and Differentiation

Volumn 23, Issue 2, 2016, Pages 270-278

  Hayano, M ^a   Yang, W S ^a   Corn, C K ^a   Pagano, N C ^a   Stockwell, B R ^a  

^a Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID TRANSFER RNA LIGASE; CYSTATHIONINE; CYSTEINE TRANSFER RNA; CYSTEINE TRANSFER RNA SYNTHETASE; CYSTINE; ERASTIN; GLUTAMIC ACID; PROTEIN INHIBITOR; REACTIVE OXYGEN METABOLITE; SERINE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; CYSTEINYL-TRNA SYNTHETASE; PIPERAZINE DERIVATIVE;

AMINO ACID SYNTHESIS; ANIMAL CELL; ARTICLE; CELL DEATH; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; ESSENTIAL GENE; FERROPTOSIS; GENE EXPRESSION REGULATION; GENE SILENCING; GENETIC SCREENING; HOMEOSTASIS; IRON METABOLISM; NONHUMAN; PRIORITY JOURNAL; RAT; SENSITIZATION; SULFATION; TRANSSULFURATION; UPREGULATION; ANIMAL; APOPTOSIS; BIOSYNTHESIS; DRUG RESISTANCE; GENETICS; HUMAN; METABOLISM; PC12 CELL LINE; SIGNAL TRANSDUCTION;

AMINO ACYL-TRNA SYNTHETASES; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BIOSYNTHETIC PATHWAYS; CYSTINE; DRUG RESISTANCE, NEOPLASM; GENE KNOCKDOWN TECHNIQUES; GLUTAMIC ACID; HUMANS; PC12 CELLS; PIPERAZINES; RATS; REACTIVE OXYGEN SPECIES; SERINE; SIGNAL TRANSDUCTION;

EID: 84954379174     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/cdd.2015.93     Document Type: Article

References (25)

1. Vila M, Przedborski S. Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci 2003; 4: 365-375.
2. Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C, De Zen F et al. Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci USA 2014; 111: 16836-16841.
3. Friedmann Angeli JP, 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: 1180-1191.
4. Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc 2014; 136: 4551-4556.
5. Bannai S, Sato H, Ishii T, Sugita Y. Induction of cystine transport activity in human fibroblasts by oxygen. J Biol Chem 1989; 264: 18480-18484.
6. 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: 317-331.
7. Yang W, Stockwell B. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol 2008; 15: 234-245.
8. Dolma S, Lessnick S, Hahn W, Stockwell B. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 2003; 3: 285-296.
9. Yagoda N, von Rechenberg M, Zaganjor E, Bauer A, Yang W, Fridman D et al. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 2007; 447: 864-868.
10. Louandre C, Ezzoukhry Z, Godin C, Barbare J-C, Mazière J-C, Chauffert B et al. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib. Int J Cancer 2013; 133: 1732-1742.
11. 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.
12. Dixon S, Lemberg K, Lamprecht M, Skouta R, Zaitsev E, Gleason C et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149: 1060-1072.
13. Boutros M, Bras LP, Huber W. Analysis of cell-based RNAi screens. Genome Biol 2006; 7: R66.
14. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA. Creation of human tumour cells with defined genetic elements. Nature 1999; 400:464-468.
15. Yao P, Fox P. Aminoacyl-tRNA synthetases in medicine and disease. EMBO Mol Med 2013; 5: 332-343.
16. Abeles RH, Walsh CT. Acetylenic enzyme inactivators. Inactivation of gamma-cystathionase, in vitro and in vivo, by propargylglycine. J Am Chem Soc 1973; 95: 6124-6125.
17. Dickhout JG, Carlisle RE, Jerome DE, Mohammed-Ali Z, Jiang H, Yang G et al. Integrated stress response modulates cellular redox state via induction of cystathionine gamma-lyase: cross-talk between integrated stress response and thiol metabolism. J Biol Chem 2012; 287: 7603-7614.
18. Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J et al. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol 2012; 8: 311-317.
19. Guo M, Yang XL, Schimmel P. New functions of aminoacyl-tRNA synthetases beyond translation. Nat Rev Mol Cell Biol 2010; 11: 668-674.
20. Pereira CM, Oliveira CR. Glutamate toxicity on a PC12 cell line involves glutathione (GSH) depletion and oxidative stress. Free Radic Biol Med 1997; 23: 637-647.
21. Ishii T, Bannai S, Sugita Y. 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 1981; 256: 12387-12392.
22. Palii SS, Kays CE, Deval C, Bruhat A, Fafournoux P, Kilberg MS. Specificity of amino acid regulated gene expression: analysis of genes subjected to either complete or single amino acid deprivation. Amino Acids 2009; 37: 79-88.
23. Mason RP, Casu M, Butler N, Breda C, Campesan S, Clapp J et al. Glutathione peroxidase activity is neuroprotective in models of Huntington's disease. Nat Genet 2013; 45: 1249-1254.
24. Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM et al. Cystathionine gamma-lyase deficiency mediates neurodegeneration in Huntington's disease. Nature 2014; 509: 96-100.
25. Hurdle JG, O'Neill AJ, Chopra I. Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents. Antimicrob Agents Chemother 2005; 49: 4821-4833.