RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Abstract
Necrosis can be induced by stimulating death receptors with tumor necrosis factor (TNF) or other agonists; however, the underlying mechanism differentiating necrosis from apoptosis is largely unknown. We identified the protein kinase receptor-interacting protein 3 (RIP3) as a molecular switch between TNF-induced apoptosis and necrosis in NIH 3T3 cells and found that RIP3 was required for necrosis in other cells. RIP3 did not affect RIP1-mediated apoptosis but was required for RIP1-mediated necrosis and the enhancement of necrosis by the caspase inhibitor zVAD. By activating key enzymes of metabolic pathways, RIP3 regulates TNF-induced reactive oxygen species production, which partially accounts for RIP3's ability to promote necrosis. Our data suggest that modulation of energy metabolism in response to death stimuli has an important role in the choice between apoptosis and necrosis.
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Excess TNF-α may induce apoptosis and necrosis of infected macrophages via stimulation of receptor-interacting serine-threonine kinases 1 and 3 and excessive radical formation.
“However, excess TNF-α may have the opposite effect by inducing apoptosis and necrosis of infected macrophages via stimulation of receptor-interacting serine-threonine kinases 1 and 3 (RIP1 and RIP3) and excessive radical formation (64–66).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [65]
Cites
Chemical 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
Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.-L., Schneider, P., Seed, B., & Tschopp, J. (2000) · Nature Immunology · doi:10.1038/82732 · Cited by 1,932 · see citing works
Cell death by necrosis: towards a molecular definition
Golstein, P., & Kroemer, G. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.001 · Cited by 1,044 · see citing works
Hitomi, J., Christofferson, D. E., Ng, A., Yao, J., Degterev, A., Xavier, R. J., & Yuan, J. (2008) · Cell · doi:10.1016/j.cell.2008.10.044 · Cited by 989 · see citing works
Schulze‐Osthoff, K., Bakker, A. C., Vanhaesebroeck, B., Beyaert, R., Jacob, W. A., & Fiers, W. C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42768-8 · Cited by 935 · see citing works
Vercammen, D., Beyaert, R., Denecker, G., Goossens, V., Loo, G., Declercq, W., Grooten, J., Fiers, W., & Vandenabeele, P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.9.1477 · Cited by 925 · see citing works
Necrotic death as a cell fatePreprint
Zong, W., & Thompson, C. B. (2006) · Genes & Development · doi:10.1101/gad.1376506 · Cited by 920 · see citing works
Festjens, N., Vanden Berghe, T., & Vandenabeele, P. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.06.014 · Cited by 710 · see citing works
Goossens, V., Grooten, J., Vos, K. J. D., & Fiers, W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8115 · Cited by 595 · see citing works
Expansion and evolution of cell death programmes
Degterev, A., & Yuan, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2393 · Cited by 552 · see citing works
Newton, K., Sun, X., & Dixit, V. M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.4.1464-1469.2004 · Cited by 544 · see citing works
Chan, F. K.-M., Shisler, J. L., Bixby, J. G., Felices, M., Zheng, L., APPEL, M. C., Orenstein, J. O., Moss, B., & Lenardo, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305633200 · Cited by 463 · see citing works
Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain
Feng, S., Yang, Y., Mei, Y., Ma, L., Zhu, D.-E., Höti, N., Castanares, M. A., & Wu, M. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.05.016 · Cited by 445 · see citing works
Lin, Y., Choksi, S., Shen, H., Yang, Q., Hur, G. M., Kim, Y. S., Tran, J. H., Nedospasov, S. A., & Liu, Z.-G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313141200 · Cited by 411 · see citing works
RIP3, a Novel Apoptosis-inducing Kinase
Sun, X., Lee, J., Navas, T. A., Baldwin, D. T., Stewart, T. A., & Dixit, V. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.24.16871 · Cited by 240 · see citing works
Inhibition of ADP/ATP Exchange in Receptor-Interacting Protein-Mediated Necrosis
Temkin, V., Huang, Q., Liu, H., Osada, H., & Pope, R. M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.6.2215-2225.2006 · Cited by 201 · see citing works
Meylan, E., Martinon, F., Thome, M., Gschwendt, M., & Tschopp, J. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf236 · Cited by 140 · see citing works
Kasof, G. M., Prosser, J. C., Liu, D., Lorenzi, M. V., & Gomes, B. C. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01473-3 · Cited by 120 · see citing works
The Oxidative Metabolism of Glutamine
Goossens, V., Grooten, J., & Fiers, W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.1.192 · Cited by 91 · see citing works
Lüschen, S., Ussat, S., Scherer, G., Kabelitz, D., & Adam‐Klages, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003280200 · Cited by 88 · see citing works
Orphan Nuclear Receptor Nur77 Is Involved in Caspase-independent Macrophage Cell Death
Kim, S. O., Ono, K., Tobias, P. S., & Han, J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021842 · Cited by 87 · see citing works
Self-citationThe extrinsic cell death pathway and the élan mortel
Wallach, D., Kang, T.-B., & Kovalenko, A. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.41 · Cited by 48 · see citing works
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Galluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421 · see citing works
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382 · see citing works
ROS in cancer therapy: the bright side of the moon
Perillo, B., Di Donato, M., Pezone, A., Di Zazzo, E., Giovannelli, P., Galasso, G., Castoria, G., & Migliaccio, A. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0384-2 · Cited by 2,176 · see citing works
Glutaminolysis 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
The Science of Stroke: Mechanisms in Search of Treatments
Moskowitz, M. A., Lo, E. H., & Iadecola, C. (2010) · Neuron · doi:10.1016/j.neuron.2010.07.002 · Cited by 1,930 · 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
Necroptosis: 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
Crosstalk between apoptosis.; necrosis and autophagy
Nikoletopoulou, V., Markaki, M., Palikaras, K., & Tavernarakis, N. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.001 · Cited by 1,366 · see citing works
Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis
Cai, Z., Jitkaew, S., Zhao, J., Chiang, H.-C., Choksi, S., Liu, J., Ward, Y., Wu, L.-G., & Liu, Z.-G. (2014) · Nature Cell Biology · doi:10.1038/ncb2883 · Cited by 1,322 · see citing works
Catalytic 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 · see citing works
Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222 · see citing works
Synchronized renal tubular cell death involves ferroptosis
Linkermann, A., Skouta, R., Himmerkus, N., Mulay, S. R., Dewitz, C., De Zen, F., Prokai, A., Zuchtriegel, G., Krombach, F., Welz, P.-S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415518111 · Cited by 1,126 · see citing works
Linkermann, A., & Green, D. R. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1310050 · Cited by 1,103 · see citing works
Pyroptosis versus necroptosis: similarities, differences, and crosstalk
Frank, D., & Vince, J. E. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0212-6 · Cited by 1,062 · see citing works
RIP3 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
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016 · see citing works
Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.137 · Cited by 1,002 · see citing works
Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989 · see citing works
TNF and ROS crosstalk in inflammation
Blaser, H., Dostert, C., Mak, T. W., & Brenner, D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.12.002 · Cited by 1,008 · see citing works
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998 · see citing works
Toll-like Receptor 3-mediated Necrosis via TRIF, RIP3, and MLKL
Kaiser, W. J., Sridharan, H., Huang, C., Mandal, P., Upton, J. W., Gough, P. J., Sehon, C. A., Marquis, R. W., Bertin, J., & Mocarski, E. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.462341 · Cited by 959 · see citing works
Chen, X., He, W.-T., Hu, L., Li, J., Fang, Y., Wang, X., Xu, X., Wang, Z., Huang, K., & Han, J. (2016) · Cell Research · doi:10.1038/cr.2016.100 · Cited by 831 · see citing works
Self-citationUpton, J. W., Kaiser, W. J., & Mocarski, E. S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.016 · Cited by 758 · 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
Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD
Mizumura, K., Cloonan, S. M., Nakahira, K., Bhashyam, A. R., Cervo, M., Kitada, T., Glass, K., Owen, C. A., Mahmood, A., Washko, G. R., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74985 · Cited by 611 · see citing works
RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS
Ito, Y., Ofengeim, D., Najafov, A., Das, S., Saberi, S., Li, Y., Hitomi, J., Zhu, H., Chen, H., Mayo, L., et al. (2016) · Science · doi:10.1126/science.aaf6803 · Cited by 606 · see citing works
Roca, F. J., & Ramakrishnan, L. (2013) · Cell · doi:10.1016/j.cell.2013.03.022 · Cited by 592 · 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 · see citing works
Initiation and execution mechanisms of necroptosis: an overview
Grootjans, S., Vanden Berghe, T., & Vandenabeele, P. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.65 · Cited by 566 · see citing works
Apoptosis and necroptosis in the liver: a matter of life and death
Schwabe, R. F., & Luedde, T. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0065-y · Cited by 582 · see citing works
Christgen, S., Zheng, M., Kesavardhana, S., Karki, R., Malireddi, R. K. S., Banoth, B., Place, D. E., Briard, B., Sharma, B. R., Tuladhar, S., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00237 · Cited by 588 · see citing works
Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut
Vaccaro, A., Kaplan Dor, Y., Nambara, K., Pollina, E. A., Lin, C., Greenberg, M. E., & Rogulja, D. (2020) · Cell · doi:10.1016/j.cell.2020.04.049 · Cited by 541 · see citing works
Virus Inhibition of RIP3-Dependent Necrosis
Upton, J. W., Kaiser, W. J., & Mocarski, E. S. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.03.006 · Cited by 559 · see citing works
Wang, Y., & Kanneganti, T.-D. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.07.038 · Cited by 545 · see citing works
Regulated cell death and inflammation: an auto-amplification loop causes organ failure
Linkermann, A., Stockwell, B. R., Krautwald, S., & Anders, H.-J. (2014) · Nature Reviews Immunology · doi:10.1038/nri3743 · Cited by 522 · see citing works
Caspase 8 inhibits programmed necrosis by processing CYLD
O’Donnell, M. A., Perez-Jimenez, E., Oberst, A., Ng, A., Massoumi, R., Xavier, R., Green, D. R., & Ting, A. T. (2011) · Nature Cell Biology · doi:10.1038/ncb2362 · Cited by 494 · see citing works
Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine
Li, C., Lee, A., Grigoryan, L., Arunachalam, P. S., Scott, M. K. D., Trisal, M., Wimmers, F., Sanyal, M., Weidenbacher, P. A., Feng, Y., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01163-9 · Cited by 505 · see citing works
Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation
Vince, J. E., Wong, W. W.-L., Gentle, I., Lawlor, K. E., Allam, R., O'Reilly, L., Mason, K., Gross, O., Ma, S., Guarda, G., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.012 · Cited by 491 · see citing works
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453 · see citing works
Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium
Günther, C., Neumann, H., Neurath, M. F., & Becker, C. (2013) · Gut · doi:10.1136/gutjnl-2011-301364 · Cited by 462 · see citing works
Dying cells actively regulate adaptive immune responses
Yatim, N., Cullen, S., & Albert, M. L. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.9 · Cited by 442 · see citing works
Caspase-8 Blocks Kinase RIPK3-Mediated Activation of the NLRP3 Inflammasome
Kang, T.-B., Yang, S.-H., Toth, B., Kovalenko, A., & Wallach, D. (2013) · Immunity · doi:10.1016/j.immuni.2012.09.015 · Cited by 419 · see citing works
Necroptosis in health and diseases
Zhou, W., & Yuan, J. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.07.013 · Cited by 414 · see citing works
RIPK1 inhibits ZBP1-driven necroptosis during development
Newton, K., Wickliffe, K. E., Maltzman, A., Dugger, D. L., Strasser, A., Pham, V. C., Lill, J. R., Roose-Girma, M., Warming, S., Solon, M., et al. (2016) · Nature · doi:10.1038/nature20559 · Cited by 390 · see citing works
Autophagy in acute kidney injury
Kaushal, G. P., & Shah, S. V. (2016) · Kidney International · doi:10.1016/j.kint.2015.11.021 · Cited by 389 · see citing works
Die another way – non-apoptotic mechanisms of cell death
Tait, S. W. G., Ichim, G., & Green, D. R. (2014) · Journal of Cell Science · doi:10.1242/jcs.093575 · Cited by 366 · see citing works
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365 · see citing works
TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation
Jouan-Lanhouet, S., Arshad, M. I., Piquet-Pellorce, C., Martin-Chouly, C., Le Moigne-Muller, G., Van Herreweghe, F., Takahashi, N., Sergent, O., Lagadic-Gossmann, D., Vandenabeele, P., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.90 · Cited by 357 · see citing works
Dickens, L. S., Boyd, R. S., Jukes-Jones, R., Hughes, M. A., Robinson, G. L., Fairall, L., Schwabe, J. W. R., Cain, K., & MacFarlane, M. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.004 · Cited by 349 · see citing works
Mechanisms of drug-induced liver injury
Yuan, L., & Kaplowitz, N. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2013.07.002 · Cited by 322 · see citing works
Moquin, D. M., McQuade, T., & Chan, F. K.-M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076841 · Cited by 320 · see citing works
RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis
Takahashi, N., Vereecke, L., Bertrand, M. J. M., Duprez, L., Berger, S. B., Divert, T., Gonçalves, A., Sze, M., Gilbert, B., Kourula, S., et al. (2014) · Nature · doi:10.1038/nature13706 · Cited by 318 · see citing works
Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury
Roychowdhury, S., McMullen, M. R., Pisano, S. G., Liu, X., & Nagy, L. E. (2013) · Hepatology · doi:10.1002/hep.26200 · Cited by 304 · see citing works
Widespread Mitochondrial Depletion via Mitophagy Does Not Compromise Necroptosis
Tait, S. W. G., Oberst, A., Quarato, G., Milasta, S., Haller, M., Wang, R., Karvela, M., Ichim, G., Yatim, N., Albert, M. L., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.034 · Cited by 303 · 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
Karch, J., Kwong, J. Q., Burr, A. R., Sargent, M. A., Elrod, J. W., Peixoto, P. M., Martinez-Caballero, S., Osinska, H., Cheng, E. H.-Y., Robbins, J., et al. (2013) · eLife · doi:10.7554/elife.00772 · Cited by 290 · see citing works
“RIP1 is able to interact with RIP3 in controlling necroptosis (Cho et al., 2009; He et al., 2009; Zhang et al., 2009).”
BackgroundTargeting macrophage necroptosis for therapeutic and diagnostic interventions in atherosclerosis
Karunakaran, D., Geoffrion, M., Wei, L., Gan, W., Richards, L., Shangari, P., DeKemp, E. M., Beanlands, R. A., Perisic, L., Maegdefessel, L., et al. (2016) · Science Advances · doi:10.1126/sciadv.1600224 · Cited by 293 · see citing works
Molecular 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
Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production
Fortes, G. B., Alves, L. S., de Oliveira, R., Dutra, F. F., Rodrigues, D., Fernandez, P. L., Souto-Padron, T., De Rosa, M. J., Kelliher, M., Golenbock, D., et al. (2012) · Blood · doi:10.1182/blood-2011-08-375303 · Cited by 246 · see citing works
Alvarez-Diaz, S., Dillon, C. P., Lalaoui, N., Tanzer, M. C., Rodriguez, D. A., Lin, A., Lebois, M., Hakem, R., Josefsson, E. C., O’Reilly, L. A., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.07.016 · Cited by 242 · see citing works
Lytic cell death in metabolic liver disease
Gautheron, J., Gores, G. J., & Rodrigues, C. M. P. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.04.001 · Cited by 225 · see citing works
The ‘complexities’ of life and death: Death receptor signalling platforms
Dickens, L. S., Powley, I. R., Hughes, M. A., & MacFarlane, M. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.04.005 · Cited by 208 · see citing works
Sonodynamic therapy-derived multimodal synergistic cancer therapy
Xu, M., Zhou, L., Zheng, L., Zhou, Q., Liu, K., Mao, Y., & Song, S. (2021) · Cancer Letters · doi:10.1016/j.canlet.2020.10.037 · Cited by 211 · see citing works
Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals
Maeda, A., & Fadeel, B. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.277 · Cited by 201 · see citing works
Xia, B., Fang, S., Chen, X., Hu, H., Chen, P., Wang, H., & Gao, Z. (2016) · Cell Research · doi:10.1038/cr.2016.26 · Cited by 202 · see citing works
Ppm1b negatively regulates necroptosis through dephosphorylating Rip3
Chen, W., Wu, J., Li, L., Zhang, Z., Ren, J., Liang, Y., Chen, F., Yang, C., Zhou, Z., Sean Su, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3120 · Cited by 161 · see citing works
Self-citationProtective Roles for Caspase-8 and cFLIP in Adult Homeostasis
Weinlich, R., Oberst, A., Dillon, C. P., Janke, L. J., Milasta, S., Lukens, J. R., Rodriguez, D. A., Gurung, P., Savage, C., Kanneganti, T. D., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.045 · Cited by 157 · see citing works
Lee, E., Song, C.-H., Bae, S.-J., Ha, K.-T., & Karki, R. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01069-y · Cited by 164 · see citing works
Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death
Taft, J., Markson, M., Legarda, D., Patel, R., Chan, M., Malle, L., Richardson, A., Gruber, C., Martín-Fernández, M., Mancini, G. M. S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.026 · Cited by 151 · see citing works
Modulatory profiling identifies mechanisms of small molecule-induced cell death
Wolpaw, A. J., Shimada, K., Skouta, R., Welsch, M. E., Akavia, U. D., Pe'er, D., Shaik, F., Bulinski, J. C., & Stockwell, B. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106149108 · Cited by 133 · see citing works
Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis
Zhao, X. M., Chen, Z., Zhao, J. B., Zhang, P. P., Pu, Y. F., Jiang, S. H., Hou, J. J., Cui, Y. M., Jia, X. L., & Zhang, S. Q. (2016) · Cell Death & Disease · doi:10.1038/cddis.2015.390 · Cited by 135 · see citing works
The NLRP3 inflammasome renders cell death pro-inflammatory
Gaidt, M. M., & Hornung, V. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.11.013 · Cited by 124 · see citing works
Lu, J. V., Weist, B. M., van Raam, B. J., Marro, B. S., Nguyen, L. V., Srinivas, P., Bell, B. D., Luhrs, K. A., Lane, T. E., Salvesen, G. S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102779108 · Cited by 122 · see citing works
The regulation of cancer cell death and metabolism by extracellular matrix attachment
Buchheit, C. L., Rayavarapu, R. R., & Schafer, Z. T. (2012) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2012.04.007 · Cited by 115 · see citing works
HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis
Park, H.-H., Park, S.-Y., Mah, S., Park, J.-H., Hong, S.-S., Hong, S., & Kim, Y.-S. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0152-8 · Cited by 110 · see citing works
Jhingran, A., Kasahara, S., Shepardson, K. M., Junecko, B. A. F., Heung, L. J., Kumasaka, D. K., Knoblaugh, S. E., Lin, X., Kazmierczak, B. I., Reinhart, T. A., et al. (2015) · PLOS Pathogens · doi:10.1371/journal.ppat.1004589 · Cited by 108 · see citing works
Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration
Cai, Z., Zhang, A., Choksi, S., Li, W., Li, T., Zhang, X.-M., & Liu, Z.-G. (2016) · Cell Research · doi:10.1038/cr.2016.87 · Cited by 103 · see citing works
TRAF2 is a biologically important necroptosis suppressor
Petersen, S. L., Chen, T. T., Lawrence, D. A., Marsters, S. A., Gonzalvez, F., & Ashkenazi, A. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.35 · Cited by 99 · see citing works
Location, location, location: A compartmentalized view of TNF-induced necroptotic signaling.
Samson, A. L., Garnish, S. E., Hildebrand, J. M., & Murphy, J. M. (2021) · Science Signaling · doi:10.1126/scisignal.abc6178 · Cited by 82 · see citing works
An Overview of Pathways of Regulated Necrosis in Acute Kidney Injury
Kers, J., Leemans, J. C., & Linkermann, A. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.03.002 · Cited by 80 · see citing works
2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter
Yang, Z., Jiang, B., Wang, Y., Ni, H., Zhang, J., Xia, J., Shi, M., Hung, L.-M., Ruan, J., Mak, T. W., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.012 · Cited by 78 · see citing works
Self-citationThe Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate
Tortola, L., Nitsch, R., Bertrand, M. J. M., Kogler, M., Redouane, Y., Kozieradzki, I., Uribesalgo, I., Fennell, L. M., Daugaard, M., Klug, H., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.032 · Cited by 64 · see citing works
Nikseresht, S., Khodagholi, F., & Ahmadiani, A. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.27055 · Cited by 58 · see citing works
Interleukin-1α and brain inflammation
Brough, D., & Denes, A. (2015) · IUBMB Life · doi:10.1002/iub.1377 · Cited by 54 · see citing works
Molecular mechanisms of necroptosis and relevance for neurodegenerative diseases.
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.12.006 · Cited by 51 · see citing works
Kalita, B., Utkin, Y. N., & Mukherjee, A. K. (2022) · Toxins · doi:10.3390/toxins14120839 · Cited by 50 · see citing works
Zhao, Q., Yu, X., Zhang, H., Liu, Y., Zhang, X., Wu, X., Xie, Q., Li, M., Ying, H., & Zhang, H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.011 · Cited by 49 · see citing works
Huai, J., Vögtle, F.-N., Jöckel, L., Li, Y., Kiefer, T., Ricci, J.-E., & Borner, C. (2013) · Journal of Cell Science · doi:10.1242/jcs.129999 · Cited by 43 · see citing works
Coupienne, I., Fettweis, G., & Piette, J. (2011) · Lasers in Surgery and Medicine · doi:10.1002/lsm.21088 · Cited by 41 · see citing works
Wang, Z., Feng, J., Yu, J., & Chen, G. (2019) · Journal of Cell Science · doi:10.1242/jcs.227777 · Cited by 35 · see citing works
Zhu, Z., Zhang, X., Pan, Q., Zhang, L., & Chai, J. (2023) · Liver Research · doi:10.1016/j.livres.2023.11.003 · Cited by 38 · see citing works
RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death
Fettweis, G., Di Valentin, E., L'homme, L., Lassence, C., Dequiedt, F., Fillet, M., Coupienne, I., & Piette, J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.10.014 · Cited by 26 · see citing works
Bencze, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010362 · Cited by 20 · see citing works
TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3
Chang, X., Wang, L., Wang, Z., Wu, S., Zhu, X., Hu, S., Wang, Y., Yu, J., & Chen, G. (2017) · Scientific Reports · doi:10.1038/s41598-017-16390-6 · Cited by 13 · see citing works
- Authors
- Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J.
- Affiliations
- Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
- Xiamen University (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Corresponding author
- Han, Jiahuai
- Venue
- Science
- Published
- 2009-07-17
- Volume
- 325
- Issue
- 5938
- Pages
- 332-336
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2060204808
- Cited by
- 1,931
- References
- 22
- Citations by year
- 2026: 52 · 2025: 106 · 2024: 95 · 2023: 115 · 2022: 142 · 2021: 135 · 2020: 109 · 2019: 105 · 2018: 124 · 2017: 131 · 2016: 140 · 2015: 128 · 2014: 174 · 2013: 105 · 2012: 107
- FWCI
- 36.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Social Sciences › Anthropology › Death, Funerary Practices, and Mourning
- Keywords
- RIPK3, necroptosis, TNF-induced cell death, apoptosis, energy metabolism, RIPK1, reactive oxygen species, death receptor signaling, programmed cell death
- MeSH terms
- Amino Acid Chloromethyl Ketones, Animals, Cell Line, Energy Metabolism, Glutamate Dehydrogenase, Glutamate-Ammonia Ligase, Necrosis, Tumor Necrosis Factor-alpha, Apoptosis, Reactive Oxygen Species, Glycogen Phosphorylase, RNA Interference, NIH 3T3 Cells, Mice, Receptor-Interacting Protein Serine-Threonine Kinases
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