Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Mar:133:130-143.
doi: 10.1016/j.freeradbiomed.2018.09.043. Epub 2018 Sep 28.

The development of the concept of ferroptosis

Tal Hirschhorn  1 , Brent R Stockwell  2
Affiliations
Review

The development of the concept of ferroptosis

Tal Hirschhorn et al. Free Radic Biol Med. 2019 Mar.

Abstract

The term ferroptosis was coined in 2012 to describe an iron-dependent regulated form of cell death caused by the accumulation of lipid-based reactive oxygen species; this type of cell death was found to have molecular characteristics distinct from other forms of regulated cell death. Features of ferroptosis have been observed periodically over the last several decades, but these molecular features were not recognized as evidence of a distinct form of cell death until recently. Here, we describe the history of observations consistent with the current definition of ferroptosis, as well as the advances that contributed to the emergence of the concept of ferroptosis. We also discuss recent implications and applications of manipulations of the ferroptotic death pathway.

Keywords: Cell death; Chemical biology; Cysteine; Ferroptosis; Iron; Lipid peroxidation; Metabolism.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Ferroptosis-related scientific discoveries before it was termed.
Schematic timeline highlights key discoveries that contributed to the emergence of the concept of ferroptosis (green) and important observations that are consistent with the current definition of ferroptosis (blue), before it ferroptosis termed.
See this image and copyright information in PMC

Comment in

References

    1. Kerr JFR, A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes, J. Pathol. Bacteriol 90 (1965) 419–435. doi:10.1002/path.1700900210. - DOI - PubMed
    1. Lockshin RA, Williams CM, Programmed cell death—II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths, J. Insect Physiol 10 (1964) 643– 649. doi:10.1016/0022-1910(64)90034-4. - DOI
    1. Lockshin RA, Williams CM, Programmed cell death—I. Cytology of degeneration in the intersegmental muscles of the Pernyi silkmoth, J. Insect Physiol 11 (1965) 123–133. doi:10.1016/0022-1910(65)90099-5. - DOI - PubMed
    1. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, Candi E, Carmona-Gutierrez D, Cecconi F, Chan FK-M, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Cohen GM, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D’Angiolella V, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin K-M, DeBerardinis RJ, Deshmukh M, Di Daniele N, Di Virgilio F, Dixit VM, Dixon SJ, Duckett CS, Dynlacht BD, El-Deiry WS, Elrod JW, Fimia GM, Fulda S, García-Sáez AJ, Garg AD, Garrido C, Gavathiotis E, Golstein P, Gottlieb E, Green DR, Greene LA, Gronemeyer H, Gross A, Hajnoczky G, Hardwick JM, Harris IS, Hengartner MO, Hetz C, Ichijo H, Jäättelä M, Joseph B, Jost PJ, Juin PP, Kaiser WJ, Karin M, Kaufmann T, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Knight RA, Kumar S, Lee SW, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, López-Otín C, Lowe SW, Luedde T, Lugli E, MacFarlane M, Madeo F, Malewicz M, Malorni W, Manic G, Marine J-C, Martin SJ, Martinou J-C, Medema JP, Mehlen P, Meier P, Melino S, Miao EA, Molkentin JD, Moll UM, Muñoz-Pinedo C, Nagata S, Nuñez G, Oberst A, Oren M, Overholtzer M, Pagano M, Panaretakis T, Pasparakis M, Penninger JM, Pereira DM, Pervaiz S, Peter ME, Piacentini M, Pinton P, Prehn JHM, Puthalakath H, Rabinovich GA, Rehm M, Rizzuto R, Rodrigues CMP, Rubinsztein DC, Rudel T, Ryan KM, Sayan E, Scorrano L, Shao F, Shi Y, Silke J, Simon H-U, Sistigu A, Stockwell BR, Strasser A, Szabadkai G, Tait SWG, Tang D, Tavernarakis N, Thorburn A, Tsujimoto Y, Turk B, Vanden Berghe T, Vandenabeele P, Vander Heiden MG, Villunger A, Virgin HW, Vousden KH, Vucic D, Wagner EF, Walczak H, Wallach D, Wang Y, Wells JA, Wood W, Yuan J, Zakeri Z, Zhivotovsky B, Zitvogel L, Melino G, Kroemer G, Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018, Cell Death Differ 25 (2018) 486–541. doi:10.1038/s41418-017-0012-4. - DOI - PMC - PubMed
    1. Chavez-Reyes A, Parant JM, Amelse LL, de O RM. Luna SJ Korsmeyer G Lozano, Switching Mechanisms of Cell Death in mdm2- and mdm4-null Mice by Deletion of p53 Downstream Targets, Cancer Res 63 (2003) 8664–8669. - PubMed

Publication types