Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis

Nature Chemical Biology

Volumn 12, Issue 7, 2016, Pages 497-503

  Shimada, Kenichi ^a   Skouta, Rachid ^a,b   Kaplan, Anna ^a   Yang, Wan Seok ^a,c   Hayano, Miki ^a   Dixon, Scott J ^a,d   Brown, Lewis M ^a   Valenzuela, Carlos A ^b   Wolpaw, Adam J ^a,e   Stockwell, Brent R ^a  

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

^b UNIVERSITY OF TEXAS AT EL PASO   (United States)

^c ST JOHN'S UNIVERSITY   (United States)

^d STANFORD UNIVERSITY   (United States)

^e CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 5 TETRADECYLOXY 2 FUROIC ACID; ALPHA TOCOPHEROL; APOPTOSIS INHIBITOR; CASPASE 3; CASPASE 7; DEFEROXAMINE; FERROPTOSIS; IDEBENONE; PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE PEROXIDASE; UNCLASSIFIED DRUG; FIN56 COMPOUND; IRON; OXIME; SULFONAMIDE;

ARTICLE; CELL DEATH; CONTROLLED STUDY; DRUG MECHANISM; ENZYME DEGRADATION; ENZYME SYNTHESIS; HUMAN; LIPID METABOLISM; METABOLIC REGULATION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEGRADATION; APOPTOSIS; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; METABOLISM; STRUCTURE ACTIVITY RELATION;

APOPTOSIS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; IRON; LIPID METABOLISM; OXIMES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 84965000436     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.2079     Document Type: Article

References (37)

1. Fuchs, Y. & Steller, H. Programmed cell death in animal development and disease. Cell 147, 742-758 (2011).
2. Aravind, L., Dixit, V.M. & Koonin, E.V. The domains of death: evolution of the apoptosis machinery. Trends Biochem. Sci. 24, 47-53 (1999).
3. Degterev, A. et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4, 313-321 (2008).
4. Vanden Berghe, T., Linkermann, A., Jouan-Lanhouet, S., Walczak, H. & Vandenabeele, P. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol. 15, 135-147 (2014).
5. Kaczmarek, A., Vandenabeele, P. & Krysko, D.V. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 38, 209-223 (2013).
6. Kono, H. & Rock, K.L. How dying cells alert the immune system to danger. Nat. Rev. Immunol. 8, 279-289 (2008).
7. Skouta, R. et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J. Am. Chem. Soc. 136, 4551-4556 (2014).
8. Linkermann, A. et al. Synchronized renal tubular cell death involves ferroptosis. Proc. Natl. Acad. Sci. USA 111, 16836-16841 (2014).
9. Dixon, S.J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060-1072 (2012).
10. Dixon, S.J. et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife 3, e02523 (2014).
11. Hayano, M., Yang, W.S., Corn, C.K., Pagano, N.C. & Stockwell, B.R. Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ. 23, 270-278 (2016).
12. Yang, W.S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317-331 (2014).
13. Imai, H. & Nakagawa, Y. Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells. Free Radic. Biol. Med. 34, 145-169 (2003).
14. Linkermann, A., Stockwell, B.R., Krautwald, S. & Anders, H.-J. Regulated cell death and inflammation: an auto-amplification loop causes organ failure. Nat. Rev. Immunol. 14, 759-767 (2014).
15. Hitomi, J. et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135, 1311-1323 (2008).
16. Hahn, W.C. et al. Creation of human tumour cells with defined genetic elements. Nature 400, 464-468 (1999).
17. Wolpaw, A.J. et al. Modulatory profiling identifies mechanisms of small molecule-induced cell death. Proc. Natl. Acad. Sci. USA 108, E771-E780 (2011).
18. Degterev, A. et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 1, 112-119 (2005).
19. Takahashi, N. et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 3, e437 (2012).
20. Yang, W.S. & Stockwell, B.R. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol. 15, 234-245 (2008).
21. Shoemaker, R.H. The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer 6, 813-823 (2006).
22. Shimada, K., Hayano, M., Pagano, N.C. & Stockwell, B.R. Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity. Cell Chem. Biol. 23, 225-235 (2016).
23. Romanowska, M. et al. Effects of selenium supplementation on expression of glutathione peroxidase isoforms in cultured human lung adenocarcinoma cell lines. Lung Cancer 55, 35-42 (2007).
24. Fradejas, N. et al. Mammalian Trit1 is a tRNA([Ser]Sec)-isopentenyl transferase required for full selenoprotein expression. Biochem. J. 450, 427-432 (2013).
25. Song, J.H. et al. Deletion of Pim kinases elevates the cellular levels of reactive oxygen species and sensitizes to K-Ras-induced cell killing. Oncogene 34, 3728-3736 (2015).
26. Tansey, T.R. & Shechter, I. Structure and regulation of mammalian squalene synthase. Biochim. Biophys. Acta 1529, 49-62 (2000).
27. Liu, C.-I. et al. Structural insights into the catalytic mechanism of human squalene synthase. Acta Crystallogr. D Biol. Crystallogr. 70, 231-241 (2014).
28. Chugh, A., Ray, A. & Gupta, J.B. Squalene epoxidase as hypocholesterolemic drug target revisited. Prog. Lipid Res. 42, 37-50 (2003).
29. Gueven, N., Woolley, K. & Smith, J. Border between natural product and drug: comparison of the related benzoquinones idebenone and coenzyme Q10. Redox Biol. 4, 289-295 (2015).
30. Dixon, S.J. et al. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem. Biol. 10, 1604-1609 (2015).
31. Hirsch, H.A. et al. A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases. Cancer Cell 17, 348-361 (2010).
32. Santos, C.R. & Schulze, A. Lipid metabolism in cancer. FEBS J. 279, 2610-2623 (2012).
33. Kamphorst, J.J., Fan, J., Lu, W., White, E. & Rabinowitz, J.D. Liquid chromatography-high resolution mass spectrometry analysis of fatty acid metabolism. Anal. Chem. 83, 9114-9122 (2011).
34. Yagoda, N. et al. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447, 864-868 (2007).
35. Cholody, W.M. et al. Derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine and uses thereof. US patent application PCT/US2008/006015 (2008).
36. Backman, T.W.H., Cao, Y. & Girke, T. ChemMine tools: an online service for analyzing and clustering small molecules. Nucleic Acids Res. 39, W486-W491 (2011).
37. Alegre-Aguarón, E. et al. Growth factor priming differentially modulates components of the extracellular matrix proteome in chondrocytes and synovium-derived stem cells. PLoS One 9, e88053 (2014).