Synchronized renal tubular cell death involves ferroptosis
Open accessAbstract
Significance: Cell death by regulated necrosis causes tremendous tissue damage in a wide variety of diseases, including myocardial infarction, stroke, sepsis, and ischemia–reperfusion injury upon solid organ transplantation. Here, we demonstrate that an iron-dependent form of regulated necrosis, referred to as ferroptosis, mediates regulated necrosis and synchronized death of functional units in diverse organs upon ischemia and other stimuli, thereby triggering a detrimental immune response. We developed a novel third-generation inhibitor of ferroptosis that is the first compound in this class that is stable in plasma and liver microsomes and that demonstrates high efficacy when supplied alone or in combination therapy.
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In an oxalate-induced mouse model of AKI, evidence of inflammation was observed, and the ferroptosis inhibitor Ferrostatin-1 successfully inhibited neutrophil infiltration and the expression of pro-inflammatory cytokines such as CXCL-2 and IL-6.
“In an oxalate-induced mouse model of AKI, evidence of inflammation was observed, and the ferroptosis inhibitor Ferrostatin-1 successfully inhibited neutrophil infiltration and the expression of pro-inflammatory cytokines such as CXCL-2 and IL-6.255,256”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [255]
Ferroptosis is potentially associated with a consistent release of immunostimulatory DAMPs.
“is potentially associated with a consistent release of immunostimulatory DAMPs [540, 541]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [540]
A similar protective effect is observed in GPX4-independent models of renal ischemic or toxic injury, Parkinson disease, and other human pathologies.
“A similar protective effect is observed in GPX4-independent models of renal ischemic or toxic injury [540, 592], Parkinson disease [593], and other human pathologies [594].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [540]
Pharmacological inhibition of ferroptosis, but not necroptosis or apoptosis, protects tissues such as renal tubules from ischemia/reperfusion injury.
“the pharmacological inhibition of ferroptosis, but not necroptosis or apoptosis, protects tissues such as renal tubules from ischemia/reperfusion injury [540].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [540]
SRS16-86, a third-generation ferrostatin with greater plasma and metabolic stability, protects kidney function and extends mouse survival after renal ischemia-reperfusion injury.
“SRS16–86 is a third generation ferrostatin with increased plasma and metabolic stability; in an in vivo model of renal ischemia-reperfusion injury, SRS16–86 protected kidney function and extended mouse survival after ischemia-reperfusion injury [58].”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [58]
Ferroptosis-derived dead cells can release damage-associated molecular patterns (DAMPs) and lipid metabolites that can cause an elevation of inflammation.
“Ferroptosis-derived dead cells can release damage-associated molecular patterns (DAMPs) and lipid metabolites that can cause an elevation of inflammation [76,77].”
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Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691 · see citing works
Self-citationGuide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199 · see citing works
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713 · see citing works
Self-citationChemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068 · see citing works
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214 · see citing works
RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931 · see citing works
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735 · see citing works
Self-citationRAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels
Yagoda, N., von Rechenberg, M., Zaganjor, E., Bauer, A. J., Yang, W. S., Fridman, D. J., Wolpaw, A. J., Smukste, I., Peltier, J. M., Boniface, J. J., et al. (2007) · Nature · doi:10.1038/nature05859 · Cited by 1,631 · see citing works
Self-citationNecroptosis: The Release of Damage-Associated Molecular Patterns and Its Physiological Relevance
Kaczmarek, A., Vandenabeele, P., & Krysko, D. V. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.003 · Cited by 1,411 · see citing works
Self-citationCatalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278 · cited 1× · see citing works
“We applied active (16-86) and inactive (16-79) compounds to a model of severe ischemia–reperfusion injury (IRI), which we described before (4).”
MethodSelf-citationFerrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models
Skouta, R., Dixon, S. J., Wang, J., Dunn, D. E., Orman, M., Shimada, K., Rosenberg, P. A., Lo, D. C., Weinberg, J. M., Linkermann, A., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja411006a · Cited by 1,146 · cited 8× · see citing works
“SRS15-72B was cleared rapidly with a half-life of t1/2 = 2 min (Table S1).”
BackgroundMethodResultInfluentialSelf-citationLinkermann, A., & Green, D. R. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1310050 · Cited by 1,103 · see citing works
Self-citationRIP3 mediates the embryonic lethality of caspase-8-deficient mice
Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., Hakem, R., Caspary, T., & Mocarski, E. S. (2011) · Nature · doi:10.1038/nature09857 · Cited by 1,057 · see citing works
Linear ubiquitination prevents inflammation and regulates immune signalling
Gerlach, B., Cordier, S. M., Schmukle, A. C., Emmerich, C. H., Rieser, E., Haas, T. L., Webb, A. I., Rickard, J. A., Anderton, H., Wong, W. W.-L., et al. (2011) · Nature · doi:10.1038/nature09816 · Cited by 940 · see citing works
Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
Günther, C., Martini, E., Wittkopf, N., Amann, K., Weigmann, B., Neumann, H., Waldner, M. J., Hedrick, S. Μ., Tenzer, S., Neurath, M. F., et al. (2011) · Nature · doi:10.1038/nature10400 · Cited by 882 · see citing works
FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
Welz, P.-S., Wullaert, A., Vlantis, K., Kondylis, V., Fernández-Majada, V., Ermolaeva, M., Kirsch, P., Sterner-Kock, A., van Loo, G., & Pasparakis, M. (2011) · Nature · doi:10.1038/nature10273 · Cited by 594 · cited 1× · see citing works
“This possibility has been ruled out in non-IRI settings by conditional tissue targeting of proteins involved in the prevention of spontaneously occurring necroptosis, such as RIPK1, and components that regulate its ubiquitinylation status [linear ubiquitinylation chain assembly complex (LUBAC), cellular inhibitors of…”
BackgroundSelf-citationTwo independent pathways of regulated necrosis mediate ischemia–reperfusion injury
Linkermann, A., Bräsen, J. H., Darding, M., Jin, M. K., Sanz, A. B., Heller, J.-O., Zen, F. D., Weinlich, R., Ortíz, A., Walczak, H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305538110 · Cited by 568 · see citing works
Self-citationLinkermann, A., Chen, G., Dong, G., Kunzendorf, U., Krautwald, S., & Dong, Z. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014030262 · Cited by 564 · see citing works
Self-citationRIPK1 Blocks Early Postnatal Lethality Mediated by Caspase-8 and RIPK3
Dillon, C. P., Weinlich, R., Rodriguez, D. A., Cripps, J. G., Quarato, G., Gurung, P., Verbist, K. C., Brewer, T. L., Llambi, F., Gong, Y.-N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.018 · Cited by 562 · see citing works
Self-citationCalcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion
Mulay, S. R., Kulkarni, O. P., Rupanagudi, K. V., Migliorini, A., Darisipudi, M. N., Vilaysane, A., Muruve, D. A., Shi, Y., Munro, F., Liapis, H., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63679 · Cited by 474 · see citing works
Self-citationLinkermann, A., Bräsen, J. H., Himmerkus, N., Liu, S., Huber, T. B., Kunzendorf, U., & Krautwald, S. (2012) · Kidney International · doi:10.1038/ki.2011.450 · Cited by 462 · see citing works
Self-citationFunctional complementation between FADD and RIP1 in embryos and lymphocytes
Zhang, H., Zhou, X., McQuade, T. J., Li, J., Chan, F. K.-M., & Zhang, J. (2011) · Nature · doi:10.1038/nature09878 · Cited by 422 · see citing works
Survival Function of the FADD-CASPASE-8-cFLIPL Complex
Dillon, C. P., Oberst, A., Weinlich, R., Janke, L. J., Kang, T.-B., Ben-Moshe, T., Mak, T. W., Wallach, D., & Green, D. R. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.03.010 · Cited by 331 · cited 4× · see citing works
“A powerful approach to definitively study the involvement of cell-specific necroptosis is to delete components of the necroptosis-suppressing complex, which consists of FADD, caspase8, RIPK1, and FLIP (26, 27), and to analyze spontaneously occurring necroptosis.”
BackgroundMethodInfluentialSelf-citationNecrostatin: A Potentially Novel Cardioprotective Agent?
Smith, C., Davidson, S. M., Lim, S. Y., Simpkin, J. C., Hothersall, J. S., & Yellon, D. M. (2007) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-007-6035-1 · Cited by 330 · see citing works
Luedde, M., Lutz, M., Carter, N., Sosna, J., Jacoby, C., Vucur, M., Gautheron, J., Roderburg, C., Borg, N., Reisinger, F., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu146 · Cited by 312 · see citing works
Self-citationTraykova-Brauch, M., Schönig, K., Greiner, O., Miloud, T., Jauch, A., Bode, M., Felsher, D., Glick, A., Kwiatkowski, D., Bujard, H., et al. (2008) · Nature Medicine · doi:10.1038/nm.1865 · Cited by 297 · see citing works
Bonnet, M. C., Preukschat, D., Welz, P.-S., van Loo, G., Ermolaeva, M. A., Bloch, W., Haase, I., & Pasparakis, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.014 · Cited by 295 · see citing works
Self-citationMolecular mechanisms of regulated necrosis
Galluzzi, L., Kepp, O., Krautwald, S., Kroemer, G., & Linkermann, A. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.02.006 · Cited by 258 · see citing works
Self-citationDevelopment and application of high throughput plasma stability assay for drug discovery
Di, L., Kerns, E. H., Hong, Y., & Chen, H. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2005.03.022 · Cited by 201 · see citing works
Necroptosis in Immunity and Ischemia-Reperfusion Injury
Linkermann, A., Hackl, M. J., Kunzendorf, U., Walczak, H., Krautwald, S., & Jevnikar, A. M. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12448 · Cited by 188 · see citing works
Self-citationWong, W. W.-L., Vince, J. E., Lalaoui, N., Lawlor, K. E., Chau, D., Bankovacki, A., Anderton, H., Metcalf, D., O’Reilly, L. A., Jost, P. J., et al. (2014) · Blood · doi:10.1182/blood-2013-06-510743 · Cited by 159 · see citing works
Fas-associated death domain (FADD) is a negative regulator of T-cell receptor–mediated necroptosis
Osborn, S. L., Diehl, G. E., Han, S., Xue, L., Kurd, N. S., Hsieh, K., Cado, D., Robey, E. A., & Winoto, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005997107 · Cited by 156 · see citing works
Antigen-mediated T cell expansion regulated by parallel pathways of death
Ch’en, I. L., Beisner, D. R., Degterev, A., Lynch, C., Yuan, J., Hoffmann, A., & Hedrick, S. Μ. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808043105 · Cited by 141 · see citing works
Dichotomy between RIP1- and RIP3-Mediated Necroptosis in Tumor Necrosis Factor-α-Induced Shock
Linkermann, A., Bräsen, J. H., Zen, F. D., Weinlich, R., Schwendener, R. A., Green, D. R., Kunzendorf, U., & Krautwald, S. (2012) · Molecular Medicine · doi:10.2119/molmed.2011.00423 · Cited by 135 · see citing works
Self-citationThe RIP1-Kinase Inhibitor Necrostatin-1 Prevents Osmotic Nephrosis and Contrast-Induced AKI in Mice
Linkermann, A., Heller, J.-O., Prókai, Á., Weinberg, J. M., Zen, F. D., Himmerkus, N., Szabo, A. J., Bräsen, J. H., Kunzendorf, U., & Krautwald, S. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012121169 · Cited by 128 · see citing works
Self-citationLiedtke, C., Bangen, J., Freimuth, J., Beraza, N., Lambertz, D., Cubero, F. J., Hatting, M., Karlmark, K. R., Streetz, K. L., Krombach, G. A., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.08.037 · Cited by 121 · see citing works
Beaulieu, P. L., Gillard, J. R., Bykowski, D., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.07.074 · Cited by 83 · see citing works
Flagged first, then by citations
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- Linkermann A, Green DR (2014) Necroptosis. N Engl J Med 370(5):455-465.
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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695 · see citing works
Self-citationGalluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2239 · Cited by 4,293 · see citing works
Ferroptosis: past, present and future
Li, J., Cao, F., Yin, H.-L., Huang, Z.-J., Lin, Z.-T., Mao, N., Sun, B., & Wang, G. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-2298-2 · Cited by 4,171 · see citing works
Ferroptosis: process and function
Xie, Y., Hou, W., Song, X., Yu, Y., Huang, J., Sun, X., Kang, R., & Tang, D. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.158 · Cited by 3,727 · see citing works
Ferroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088 · see citing works
Self-citationCD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
Wang, W., Green, M., Choi, J. E., Gijón, M., Kennedy, P. D., Johnson, J. K., Liao, P., Lang, X., Kryczek, I., Sell, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1170-y · Cited by 2,880 · see citing works
Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis
Yang, W. S., Kim, K. J., Gaschler, M. M., Patel, M., Shchepinov, M. S., & Stockwell, B. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603244113 · Cited by 2,329 · see citing works
Self-citationGlutaminolysis and transferrin regulate ferroptosis
Gao, M., Monian, P., Quadri, N., Ramasamy, R., & Jiang, X. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.06.011 · Cited by 2,069 · see citing works
Sun, X., Ou, Z., Chen, R., Niu, X., Chen, D., Kang, R., & Tang, D. (2016) · Hepatology · doi:10.1002/hep.28251 · Cited by 2,012 · see citing works
Ferroptosis is an autophagic cell death process
Gao, M., Monian, P., Pan, Q., Zhang, W., Xiang, J., & Jiang, X. (2016) · Cell Research · doi:10.1038/cr.2016.95 · Cited by 1,899 · see citing works
Role of GPX4 in ferroptosis and its pharmacological implication
Seibt, T. M., Proneth, B., & Conrad, M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.014 · Cited by 1,520 · see citing works
Cao, J. Y., & Dixon, S. J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2194-1 · Cited by 1,515 · see citing works
Ferroptosis: Mechanisms and links with diseases
Yan, H.-F., Zou, T., Tuo, Q.-Z., Xu, S., Li, H., Belaidi, A. A., & Lei, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00428-9 · Cited by 1,471 · see citing works
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
“In addition, it triggers the elevated production of the pro-inflammatory cytokine IL-6.”
BackgroundInfluentialIdentification of ACSL4 as a biomarker and contributor of ferroptosis
Yuan, H., Li, X., Zhang, X., Kang, R., & Tang, D. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.124 · Cited by 1,071 · see citing works
Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
Dixon, S. J., Winter, G. E., Musavi, L. S., Lee, E. D., Snijder, B., Rebsamen, M., Superti-Furga, G., & Stockwell, B. R. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00245 · Cited by 1,043 · see citing works
Self-citationGlobal survey of cell death mechanisms reveals metabolic regulation of ferroptosis
Shimada, K., Skouta, R., Kaplan, A., Yang, W. S., Hayano, M., Dixon, S. J., Brown, L. M., Valenzuela, C. A., Wolpaw, A. J., & Stockwell, B. R. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2079 · Cited by 1,017 · see citing works
Self-citationThe Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity
Xie, Y., Zhu, S., Song, X., Sun, X., Fan, Y., Liu, J., Zhong, M., Yuan, H., Zhang, L., Billiar, T. R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.055 · Cited by 952 · see citing works
Zou, Y., Palte, M. J., Deik, A. A., Li, H., Eaton, J. K., Wang, W., Tseng, Y.-Y., Deasy, R., Kost-Alimova, M., Dančík, V., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09277-9 · Cited by 887 · see citing works
Hambright, W. S., Fonseca, R. S., Chen, L., Na, R., & Ran, Q. (2017) · Redox Biology · doi:10.1016/j.redox.2017.01.021 · Cited by 851 · see citing works
The emerging role of ferroptosis in inflammation
Sun, Y., Chen, P., Zhai, B., Zhang, M., Xiang, Y., Fang, J., Xu, S., Gao, Y., Chen, X., Sui, X., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110108 · Cited by 739 · see citing works
HSPB1 as a novel regulator of ferroptotic cancer cell death
Sun, X., Ou, Z., Xie, M., Kang, R., Fan, Y., Niu, X., Wang, H., Cao, L., & Tang, D. (2015) · Oncogene · doi:10.1038/onc.2015.32 · Cited by 666 · see citing works
Park, M. W., Cha, H. W., Kim, J., Kim, J. H., Yang, H., Yoon, S., Boonpraman, N., Yi, S. S., Yoo, I. D., & Moon, J.-S. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101947 · Cited by 683 · see citing works
“Ferroptosis-derived dead cells can release damage-associated molecular patterns (DAMPs) and lipid metabolites that can cause an elevation of inflammation [76,77].”
BackgroundKim, S. E., Zhang, L., Ma, K., Riegman, M., Chen, F., Ingold, I., Conrad, M., Turker, M. Z., Gao, M., Jiang, X., et al. (2016) · Nature Nanotechnology · doi:10.1038/nnano.2016.164 · Cited by 622 · see citing works
Regulated necrosis: disease relevance and therapeutic opportunities
Conrad, M., Angeli, J. P. F., Vandenabeele, P., & Stockwell, B. R. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.6 · Cited by 630 · see citing works
Self-citationFerroptosis Inhibition: Mechanisms and Opportunities
Angeli, J. P. F., Shah, R., Pratt, D. A., & Conrad, M. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.02.005 · Cited by 563 · see citing works
Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid–Induced AKI
Martin-Sanchez, D., Ruiz-Andres, O., Poveda, J., Carrasco, S., Cannata-Ortiz, P., Sanchez-Niño, M. D., Ruiz Ortega, M., Egido, J., Linkermann, A., Ortiz, A., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015121376 · Cited by 564 · see citing works
Self-citationIron and cancer: recent insights
Manz, D. H., Blanchette, N. L., Paul, B. T., Torti, F. M., & Torti, S. V. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13008 · Cited by 507 · see citing works
Regulation of lipid peroxidation and ferroptosis in diverse species
Conrad, M., Kagan, V. E., Bayir, H., Pagnussat, G. C., Head, B., Traber, M. G., & Stockwell, B. R. (2018) · Genes & Development · doi:10.1101/gad.314674.118 · Cited by 544 · see citing works
Self-citationAmaral, E. P., Costa, D. L., Namasivayam, S., Riteau, N., Kamenyeva, O., Mittereder, L., Mayer-Barber, K. D., Andrade, B. B., & Sher, A. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20181776 · Cited by 464 · see citing works
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Self-citationTargeting iron metabolism in drug discovery and delivery
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An essential role for functional lysosomes in ferroptosis of cancer cells
Torii, S., Shintoku, R., Kubota, C., Yaegashi, M., Torii, R., Sasaki, M., Suzuki, T., Mori, M., Yoshimoto, Y., Takeuchi, T., et al. (2016) · Biochemical Journal · doi:10.1042/bj20150658 · Cited by 349 · see citing works
Dixon, S. J. (2017) · Immunological Reviews · doi:10.1111/imr.12533 · Cited by 314 · see citing works
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Heat stress induces ferroptosis-like cell death in plants
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Self-citationDar, H. H., Tyurina, Y. Y., Mikulska-Ruminska, K., Shrivastava, I., Ting, H.-C., Tyurin, V. A., Krieger, J., St. Croix, C. M., Watkins, S., Bayir, E., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99490 · Cited by 251 · see citing works
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Youssef, L. A., Rebbaa, A., Pampou, S., Weisberg, S. P., Stockwell, B. R., Hod, E. A., & Spitalnik, S. L. (2018) · Blood · doi:10.1182/blood-2017-12-822619 · Cited by 186 · see citing works
Self-citationPathophysiological role of different tubular epithelial cell death modes in acute kidney injury
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Self-citation
- Authors
- Linkermann, A., Skouta, R., Himmerkus, N., Mulay, S. R., Dewitz, C., De Zen, F., Prokai, A., Zuchtriegel, G., Krombach, F., Welz, P.-S., Weinlich, R., Vanden Berghe, T., Vandenabeele, P., Pasparakis, M., Bleich, M., Weinberg, J. M., Reichel, C. A., Bräsen, J. H., Kunzendorf, U., Anders, H.-J., Stockwell, B. R., Green, D. R., & Krautwald, S.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- The University of Texas at El Paso (US)
- LMU Klinikum (DE)
- Clinic for Nephrology and Hypertension, Christian-Albrechts-University Kiel, 24105 Kiel, Germany;
- First Department of Pediatrics, Semmelweis University, H-1083 Budapest, Hungary;
- Institut für Chirurgische Forschung (DE)
- University of Cologne (DE)
- St. Jude Children's Research Hospital (US)
- Molecular Signaling and Cell Death Unit, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, Ghent University, 9052 Ghent, Belgium;
- Vlaams Instituut voor Biotechnologie (BE)
- University of Michigan (US)
- Leibniz University Hannover (DE)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-11-10
- Volume
- 111
- Issue
- 47
- Pages
- 16836-16841
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4250130
- OpenAlex
- W2045171661
- Cited by
- 1,126
- References
- 37
- Citations by year
- 2026: 90 · 2025: 111 · 2024: 135 · 2023: 135 · 2022: 158 · 2021: 117 · 2020: 102 · 2019: 79 · 2018: 64 · 2017: 45 · 2016: 63 · 2015: 24 · 2014: 1
- FWCI
- 35.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- Howard Hughes Medical Institute
- U.S. Department of Veterans Affairs (#I01 BX002367)
- Hearst Foundations
- Whitehall Foundation
- Pfizer
- New York State Stem Cell Science
- Deutsche Forschungsgemeinschaft (AN372/15-1, AN372/9-2)
- Fonds Wetenschappelijk Onderzoek (G.0875.11, G0C3114N, G078713N, FWO G0787.13N, FWO G.0973.11, G.0973.11, FWO G.0172.12, G.0172.12, KAN 31528711, FWO G.0875.11, G.0A45.12)
- Universiteit Gent (01M00709)
- Vlaams Instituut voor Biotechnologie (BOF09/01M00709)
- Vlaamse regering (BOF09/01M00709)
- National Institutes of Health
- National Cancer Institute (R01CA169291, R01CA097061, R01CA161061)
- National Institute of General Medical Sciences (R01GM085081)
- National Institute of Allergy and Infectious Diseases (R01AI044828)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034275, R01-DK-34275)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- ferroptosis, ischemia-reperfusion injury, acute kidney injury, necroptosis, RIPK3, FADD, caspase-8, necrostatin-1, ferrostatin-1, mitochondrial permeability transition, intravital microscopy, hypoxic injury
- MeSH terms
- Animals, Body Weight, Kidney Tubules, Reperfusion Injury, Apoptosis, Mice, Caspase 8, Fas-Associated Death Domain Protein, Receptor-Interacting Protein Serine-Threonine Kinases
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