Display options
Cite
Chen X, Li J, Kang R, et al. Ferroptosis: machinery and regulation. Autophagy. 2020;17(9):2054-2081doi: 10.1080/15548627.2020.1810918.
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021). Ferroptosis: machinery and regulation. Autophagy, 17(9), 2054-2081. https://doi.org/10.1080/15548627.2020.1810918
Chen, Xin, et al. "Ferroptosis: machinery and regulation." Autophagy vol. 17,9 (2021): 2054-2081. doi: https://doi.org/10.1080/15548627.2020.1810918
Chen X, Li J, Kang R, Klionsky DJ, Tang D. Ferroptosis: machinery and regulation. Autophagy. 2021 Sep;17(9):2054-2081. doi: 10.1080/15548627.2020.1810918. Epub 2020 Aug 26. PMID: 32804006; PMCID: PMC8496712.
Copy Download .nbib Format: NLM
Share it on

Autophagy. 2021 Sep;17(9):2054-2081. doi: 10.1080/15548627.2020.1810918. Epub 2020 Aug 26.

Ferroptosis: machinery and regulation.

Autophagy

Xin Chen, Jingbo Li, Rui Kang, Daniel J Klionsky, Daolin Tang

Affiliations

  1. Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation; the Third Affiliated Hospital; School of Basic Medical Sciences; Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  2. Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.
  3. Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.

PMID: 32804006 PMCID: PMC8496712 DOI: 10.1080/15548627.2020.1810918

Abstract

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which is controlled by integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase is the main promoter of ferroptosis by producing lipid hydroperoxides, and its function relies on the activation of ACSL4-dependent lipid biosynthesis. In contrast, the selenium-containing enzyme GPX4 is currently recognized as a central repressor of ferroptosis, and its activity depends on glutathione produced from the activation of the cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, and amino acids) and degradation pathways (macroautophagy/autophagy and the ubiquitin-proteasome system) orchestrate the complex ferroptotic response through direct or indirect regulation of iron accumulation or lipid peroxidation. Although the detailed mechanism of membrane injury during ferroptosis remains a mystery, ESCRT III-mediated plasma membrane repair can make cells resistant to ferroptosis. Here, we review the recent rapid progress in understanding the molecular mechanisms of ferroptosis and focus on the epigenetic, transcriptional, and posttranslational regulation of this process.

Keywords: Autophagy; Ferroptosis; cell death

References

  1. Front Aging Neurosci. 2016 Dec 20;8:308 - PubMed
  2. Nat Rev Mol Cell Biol. 2017 Feb;18(2):127-136 - PubMed
  3. ACS Chem Biol. 2020 Feb 21;15(2):469-484 - PubMed
  4. J Biol Chem. 2005 Nov 11;280(45):37423-9 - PubMed
  5. J Exp Med. 2015 Apr 6;212(4):555-68 - PubMed
  6. Science. 2018 Nov 23;362(6417):956-960 - PubMed
  7. Adv Mater. 2019 Dec;31(51):e1904197 - PubMed
  8. Cancer Lett. 2018 Mar 1;416:124-137 - PubMed
  9. Front Cell Dev Biol. 2020 Jun 03;8:431 - PubMed
  10. Redox Biol. 2020 Jan;28:101328 - PubMed
  11. ACS Chem Biol. 2017 Oct 20;12(10):2538-2545 - PubMed
  12. Cell. 2019 May 16;177(5):1262-1279.e25 - PubMed
  13. Free Radic Biol Med. 2018 Dec;129:454-462 - PubMed
  14. Nat Cell Biol. 2018 Oct;20(10):1181-1192 - PubMed
  15. Cell. 2019 Jan 10;176(1-2):11-42 - PubMed
  16. Cell Rep. 2016 Jan 26;14(3):411-421 - PubMed
  17. Oncogene. 2015 Nov 5;34(45):5617-25 - PubMed
  18. J Biol Chem. 2015 Jun 5;290(23):14668-78 - PubMed
  19. Cell. 2018 Jan 25;172(3):409-422.e21 - PubMed
  20. Nano Lett. 2019 Nov 13;19(11):7781-7792 - PubMed
  21. Arch Toxicol. 2019 May;93(5):1265-1279 - PubMed
  22. Redox Biol. 2020 Feb;30:101418 - PubMed
  23. Hepatology. 2016 Jan;63(1):173-84 - PubMed
  24. Cancer Gene Ther. 2021 Feb;28(1-2):55-63 - PubMed
  25. Free Radic Biol Med. 2003 Nov 1;35(9):1101-9 - PubMed
  26. Hepatology. 2021 Mar;73(3):1176-1193 - PubMed
  27. Mol Cell Oncol. 2015 May 26;2(4):e1054549 - PubMed
  28. Cancer Gene Ther. 2020 May;27(5):267-269 - PubMed
  29. ACS Cent Sci. 2016 Sep 28;2(9):653-659 - PubMed
  30. Nat Commun. 2019 Jul 17;10(1):3145 - PubMed
  31. Free Radic Biol Med. 2019 Mar;133:112-117 - PubMed
  32. Cell Signal. 2020 Aug;72:109633 - PubMed
  33. Cell Signal. 2019 Nov;63:109384 - PubMed
  34. Metallomics. 2019 May 22;11(5):982-993 - PubMed
  35. Nat Chem Biol. 2020 Mar;16(3):302-309 - PubMed
  36. Nat Commun. 2019 Apr 8;10(1):1617 - PubMed
  37. Nat Chem Biol. 2019 Dec;15(12):1137-1147 - PubMed
  38. Nat Chem Biol. 2017 Jan;13(1):91-98 - PubMed
  39. Cell Death Dis. 2016 Jul 21;7:e2307 - PubMed
  40. Cancer Res. 2019 Oct 15;79(20):5355-5366 - PubMed
  41. Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):E6806-E6812 - PubMed
  42. Commun Biol. 2018 Nov 28;1:210 - PubMed
  43. Dev Cell. 2018 Aug 20;46(4):441-455.e8 - PubMed
  44. ACS Cent Sci. 2018 Mar 28;4(3):387-396 - PubMed
  45. Cell Res. 2016 Sep;26(9):1021-32 - PubMed
  46. Genes Dev. 2016 Apr 15;30(8):918-30 - PubMed
  47. Nature. 2019 Nov;575(7784):693-698 - PubMed
  48. Cell Res. 2020 Feb;30(2):146-162 - PubMed
  49. Biochem Biophys Res Commun. 2020 Apr 30;525(2):366-371 - PubMed
  50. Autophagy. 2015;11(1):28-45 - PubMed
  51. Biochem Biophys Res Commun. 2020 Feb 5;522(2):415-421 - PubMed
  52. J Am Chem Soc. 2019 Dec 26;141(51):20407-20415 - PubMed
  53. Redox Biol. 2017 Aug;12:558-570 - PubMed
  54. Cell. 2017 Apr 6;169(2):286-300.e16 - PubMed
  55. Cell. 1998 Mar 20;92(6):725-34 - PubMed
  56. Redox Biol. 2017 Apr;11:254-262 - PubMed
  57. Science. 2000 Dec 1;290(5497):1717-21 - PubMed
  58. Cell Res. 2019 May;29(5):347-364 - PubMed
  59. Cancer Gene Ther. 2021 Feb;28(1-2):1-4 - PubMed
  60. Cell Death Differ. 2016 Feb;23(2):270-8 - PubMed
  61. Autophagy. 2019 Nov;15(11):2033-2035 - PubMed
  62. Cell Rep. 2017 Dec 5;21(10):2926-2939 - PubMed
  63. Nature. 2014 May 1;509(7498):105-9 - PubMed
  64. Phytomedicine. 2015 Oct 15;22(11):1045-54 - PubMed
  65. Blood. 2020 Aug 6;136(6):726-739 - PubMed
  66. Life Sci. 2019 Nov 15;237:116893 - PubMed
  67. Cell. 2017 Jan 26;168(3):344-361 - PubMed
  68. J Neuroinflammation. 2020 Apr 11;17(1):110 - PubMed
  69. Environ Pollut. 2019 Nov;254(Pt A):112937 - PubMed
  70. Neurobiol Dis. 2016 Oct;94:169-78 - PubMed
  71. Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2996-3005 - PubMed
  72. J Cell Biol. 2017 Dec 4;216(12):4287-4297 - PubMed
  73. Cell Metab. 2011 Nov 2;14(5):647-57 - PubMed
  74. Blood. 2016 Jan 7;127(1):139-48 - PubMed
  75. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5531-4 - PubMed
  76. J Am Chem Soc. 2014 Mar 26;136(12):4551-6 - PubMed
  77. Science. 2014 Feb 28;343(6174):1247136 - PubMed
  78. Cell Death Dis. 2019 Nov 28;10(12):902 - PubMed
  79. FEBS Open Bio. 2019 Feb 23;9(4):582-593 - PubMed
  80. EMBO J. 2006 Nov 15;25(22):5396-404 - PubMed
  81. Free Radic Biol Med. 2003 Feb 15;34(4):496-502 - PubMed
  82. Cancer Gene Ther. 2020 Sep;27(9):645-656 - PubMed
  83. Cell Host Microbe. 2018 Jul 11;24(1):97-108.e4 - PubMed
  84. Antioxid Redox Signal. 2015 Feb 1;22(4):281-93 - PubMed
  85. Free Radic Biol Med. 2019 Mar;133:162-168 - PubMed
  86. J Clin Invest. 2012 Dec;122(12):4569-79 - PubMed
  87. Biol Pharm Bull. 2020;43(3):480-487 - PubMed
  88. Cell Rep. 2019 Sep 3;28(10):2501-2508.e4 - PubMed
  89. Chem Phys Lipids. 2009 Jan;157(1):1-11 - PubMed
  90. Cancer Lett. 2018 Aug 1;428:21-33 - PubMed
  91. Oncotarget. 2017 Dec 9;8(70):114588-114602 - PubMed
  92. Cancer Res. 2018 Jul 1;78(13):3484-3496 - PubMed
  93. Toxicol Appl Pharmacol. 2019 Sep 15;379:114665 - PubMed
  94. Biochem Biophys Res Commun. 2016 Sep 23;478(3):1338-43 - PubMed
  95. Cell Rep. 2019 Feb 5;26(6):1544-1556.e8 - PubMed
  96. Cell. 2014 Jan 16;156(1-2):317-331 - PubMed
  97. Cell Death Dis. 2019 Apr 15;10(5):331 - PubMed
  98. Cell Death Differ. 2019 Nov;26(11):2284-2299 - PubMed
  99. Nature. 2017 Nov 9;551(7679):247-250 - PubMed
  100. Curr Top Med Chem. 2001 Dec;1(6):497-506 - PubMed
  101. Nutr Metab (Lond). 2016 Feb 25;13:16 - PubMed
  102. Nat Cell Biol. 2019 May;21(5):579-591 - PubMed
  103. Chem Biol. 2008 Mar;15(3):234-45 - PubMed
  104. Chem Rev. 2011 Oct 12;111(10):5866-98 - PubMed
  105. Nature. 2006 Mar 2;440(7080):96-100 - PubMed
  106. Free Radic Biol Med. 2018 Mar;117:45-57 - PubMed
  107. Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H659-H668 - PubMed
  108. J Am Chem Soc. 2018 Mar 14;140(10):3798-3808 - PubMed
  109. Nat Rev Microbiol. 2009 Feb;7(2):99-109 - PubMed
  110. Cell Rep. 2018 Jan 16;22(3):569-575 - PubMed
  111. Transfus Apher Sci. 2018 Aug;57(4):524-531 - PubMed
  112. ACS Cent Sci. 2018 Aug 22;4(8):960-970 - PubMed
  113. Sci Rep. 2018 Jan 12;8(1):574 - PubMed
  114. Nature. 2009 Apr 30;458(7242):1131-5 - PubMed
  115. Nat Cell Biol. 2014 Dec;16(12):1180-91 - PubMed
  116. Cell Death Differ. 2020 Feb;27(2):662-675 - PubMed
  117. Mol Cell Biol. 2009 Feb;29(4):1007-16 - PubMed
  118. Trends Biochem Sci. 2016 Mar;41(3):274-286 - PubMed
  119. Signal Transduct Target Ther. 2020 May 8;5(1):51 - PubMed
  120. Biochem Biophys Res Commun. 2016 May 13;473(4):775-780 - PubMed
  121. Pathol Oncol Res. 2015 Sep;21(4):1115-21 - PubMed
  122. Mol Cell. 2015 Jul 16;59(2):298-308 - PubMed
  123. Free Radic Biol Med. 2020 Feb 20;148:151-161 - PubMed
  124. J Biol Chem. 1996 Mar 1;271(9):4653-8 - PubMed
  125. Mol Psychiatry. 2017 Nov;22(11):1520-1530 - PubMed
  126. Biochem Biophys Res Commun. 2019 Mar 5;510(2):278-283 - PubMed
  127. Oncogenesis. 2017 Aug 14;6(8):e371 - PubMed
  128. Cell Death Differ. 2018 Aug;25(8):1457-1472 - PubMed
  129. Nature. 2017 Nov 30;551(7682):639-643 - PubMed
  130. Cancer Res. 2017 Apr 15;77(8):2064-2077 - PubMed
  131. Nat Chem. 2019 Jun;11(6):521-532 - PubMed
  132. Cell Chem Biol. 2019 May 16;26(5):623-633.e9 - PubMed
  133. Autophagy. 2007 Jul-Aug;3(4):295-9 - PubMed
  134. Cancer Cell. 2003 Mar;3(3):285-96 - PubMed
  135. Cell Death Dis. 2017 Mar 30;8(3):e2716 - PubMed
  136. JCI Insight. 2017 Apr 6;2(7):e90777 - PubMed
  137. Adv Mater. 2018 Mar;30(12):e1704007 - PubMed
  138. Cell Death Differ. 2016 Mar;23(3):369-79 - PubMed
  139. J Exp Clin Cancer Res. 2019 Sep 13;38(1):402 - PubMed
  140. Cell Chem Biol. 2020 Apr 16;27(4):436-447 - PubMed
  141. Free Radic Biol Med. 2019 Mar;133:101-111 - PubMed
  142. Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):E4966-75 - PubMed
  143. Oncogene. 2018 Oct;37(40):5435-5450 - PubMed
  144. Nature. 2019 May;569(7755):270-274 - PubMed
  145. Nat Commun. 2020 Jan 23;11(1):433 - PubMed
  146. Cell Death Differ. 2020 Jan;27(1):242-254 - PubMed
  147. Mol Cancer Res. 2020 Jan;18(1):79-90 - PubMed
  148. EMBO Rep. 2019 Jul;20(7):e47563 - PubMed
  149. Hepatology. 2016 Aug;64(2):488-500 - PubMed
  150. Theranostics. 2017 Jul 23;7(13):3293-3305 - PubMed
  151. Biochem Biophys Res Commun. 2020 Oct 22;531(4):581-587 - PubMed
  152. Cell Chem Biol. 2016 Feb 18;23(2):225-235 - PubMed
  153. Biochem Biophys Res Commun. 2020 May 7;525(3):620-625 - PubMed
  154. Cell Death Dis. 2018 Sep 26;9(10):1005 - PubMed
  155. Nat Chem Biol. 2018 May;14(5):507-515 - PubMed
  156. Biochem Biophys Res Commun. 2016 Sep 16;478(2):838-44 - PubMed
  157. Cancer Discov. 2019 Dec;9(12):1673-1685 - PubMed
  158. Biochem Biophys Res Commun. 2003 May 30;305(2):278-86 - PubMed
  159. Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3826-3836 - PubMed
  160. J Biol Chem. 2020 Jan 3;295(1):69-82 - PubMed
  161. Biochem J. 2016 Mar 15;473(6):769-77 - PubMed
  162. Curr Pathobiol Rep. 2017 Jun;5(2):153-159 - PubMed
  163. Biochem Biophys Res Commun. 2019 Nov 12;519(3):533-539 - PubMed
  164. Elife. 2014 May 20;3:e02523 - PubMed
  165. Dev Cell. 2019 Dec 2;51(5):575-586.e4 - PubMed
  166. Cell. 2017 Oct 5;171(2):273-285 - PubMed
  167. Oxid Med Cell Longev. 2020 Apr 3;2020:1675613 - PubMed
  168. Nat Rev Cancer. 2019 Jul;19(7):405-414 - PubMed
  169. J Lipid Res. 2014 Aug;55(8):1657-67 - PubMed
  170. Nat Cell Biol. 2020 Feb;22(2):225-234 - PubMed
  171. Cell Death Dis. 2019 Oct 28;10(11):822 - PubMed
  172. J Am Soc Nephrol. 2020 Feb;31(2):280-296 - PubMed
  173. Free Radic Biol Med. 2016 Feb;91:68-80 - PubMed
  174. Free Radic Biol Med. 2020 May 20;152:668-679 - PubMed
  175. Autophagy. 2019 Jan;15(1):172-173 - PubMed
  176. Nat Chem. 2017 Oct;9(10):1025-1033 - PubMed
  177. J Biol Chem. 1995 Oct 13;270(41):24209-15 - PubMed
  178. Biochem Biophys Res Commun. 2019 Jan 22;508(4):997-1003 - PubMed
  179. Cancer Res. 2019 Apr 15;79(8):1913-1924 - PubMed
  180. Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8390-8396 - PubMed
  181. Nat Chem Biol. 2017 Jan;13(1):81-90 - PubMed
  182. Cancer Cell. 2019 Jun 10;35(6):830-849 - PubMed
  183. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15774-9 - PubMed
  184. FEBS Open Bio. 2020 Apr;10(4):637-643 - PubMed
  185. Oncoscience. 2015 May 02;2(5):517-32 - PubMed
  186. Cell Rep. 2017 Aug 15;20(7):1692-1704 - PubMed
  187. Hum Mutat. 2013 Nov;34(11):1529-36 - PubMed
  188. Int J Oncol. 2018 Mar;52(3):1011-1022 - PubMed
  189. ACS Chem Biol. 2018 Apr 20;13(4):1013-1020 - PubMed
  190. Oxid Med Cell Longev. 2020 Jan 20;2020:6286984 - PubMed
  191. Antioxid Redox Signal. 2014 Apr 10;20(11):1754-69 - PubMed
  192. Biol Trace Elem Res. 1984 Aug;6(4):357-64 - PubMed
  193. Biochem Biophys Res Commun. 2018 Feb 26;497(1):233-240 - PubMed
  194. Nature. 2019 Nov;575(7784):688-692 - PubMed
  195. Biochem Biophys Res Commun. 2016 Nov 25;480(4):602-607 - PubMed
  196. ACS Cent Sci. 2017 Mar 22;3(3):232-243 - PubMed
  197. J Biol Chem. 1981 Dec 10;256(23):12387-92 - PubMed
  198. Nature. 2019 Aug;572(7769):402-406 - PubMed
  199. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7455-60 - PubMed
  200. Curr Biol. 2018 Aug 6;28(15):2388-2399.e5 - PubMed
  201. Science. 2020 Apr 3;368(6486):85-89 - PubMed
  202. Mol Cell Biol. 2009 May;29(10):2658-72 - PubMed
  203. Nat Chem Biol. 2016 Jul;12(7):497-503 - PubMed
  204. Cell Death Dis. 2019 Oct 7;10(10):755 - PubMed
  205. Mol Cell. 2019 Jan 17;73(2):354-363.e3 - PubMed
  206. Autophagy. 2020 Nov;16(11):2069-2083 - PubMed
  207. Nature. 2015 Apr 2;520(7545):57-62 - PubMed
  208. Immunol Rev. 2012 Sep;249(1):158-75 - PubMed
  209. Free Radic Biol Med. 2019 Feb 1;131:356-369 - PubMed
  210. Cell Chem Biol. 2020 Apr 16;27(4):420-435 - PubMed
  211. Mol Cell. 2017 Oct 5;68(1):224-232.e4 - PubMed
  212. Sci Rep. 2018 Mar 26;8(1):5155 - PubMed
  213. Nat Commun. 2020 May 19;11(1):2508 - PubMed
  214. Nat Commun. 2020 Mar 6;11(1):1251 - PubMed
  215. Cell Mol Life Sci. 2017 Oct;74(19):3631-3645 - PubMed
  216. ACS Cent Sci. 2020 Jan 22;6(1):41-53 - PubMed
  217. Arch Toxicol. 2018 Feb;92(2):759-775 - PubMed
  218. Cell Death Differ. 2018 Mar;25(3):486-541 - PubMed
  219. Nature. 2007 Jun 14;447(7146):864-8 - PubMed
  220. J Clin Invest. 2018 Aug 1;128(8):3341-3355 - PubMed
  221. Biochim Biophys Acta. 2015 May;1853(5):1130-44 - PubMed
  222. Cell. 2017 Oct 19;171(3):628-641.e26 - PubMed
  223. Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2672-2680 - PubMed
  224. Cell Death Differ. 2019 Nov;26(11):2329-2343 - PubMed
  225. Nat Chem Biol. 2020 May;16(5):497-506 - PubMed
  226. Biochem Biophys Res Commun. 2020 Mar 19;523(4):966-971 - PubMed
  227. Biochem Biophys Res Commun. 2018 Sep 10;503(3):1550-1556 - PubMed
  228. Hepatology. 2017 Aug;66(2):449-465 - PubMed
  229. Autophagy. 2016 Aug 2;12(8):1425-8 - PubMed
  230. Cell. 2006 Jul 14;126(1):107-20 - PubMed
  231. Gastroenterology. 2018 Apr;154(5):1480-1493 - PubMed
  232. Br J Cancer. 2020 Jan;122(2):279-292 - PubMed
  233. Cell Death Differ. 2020 Mar;27(3):1008-1022 - PubMed
  234. Autophagy. 2021 Apr;17(4):948-960 - PubMed
  235. Nat Metab. 2020 Mar;2(3):270-277 - PubMed
  236. Cell. 2015 Jul 16;162(2):441-451 - PubMed
  237. Semin Cancer Biol. 2020 Nov;66:89-100 - PubMed
  238. Cell. 2012 May 25;149(5):1060-72 - PubMed
  239. Cell Chem Biol. 2019 Mar 21;26(3):420-432.e9 - PubMed
  240. Ecotoxicol Environ Saf. 2020 May;194:110360 - PubMed
  241. Redox Biol. 2019 Jun;24:101211 - PubMed
  242. J Biol Chem. 2002 Jul 12;277(28):25617-23 - PubMed
  243. Biochem Biophys Res Commun. 2018 Sep 3;503(1):297-303 - PubMed
  244. Biochim Biophys Acta Mol Basis Dis. 2019 Sep 1;1865(9):2303-2316 - PubMed
  245. Oncogene. 2017 Oct 5;36(40):5593-5608 - PubMed
  246. Sci Adv. 2019 Jul 24;5(7):eaaw2238 - PubMed

Publication Types