The DOI matches its Crossref record; 152 of the 152 references it cites were found in a registry or an index.
Initiation and execution mechanisms of necroptosis: an overview
Open accessAbstract
Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating recruitment and activation of receptor-interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis executioner mixed lineage kinase domain-like (MLKL). In case of the TNF family members, the initiator is the survival- and cell death-regulating RIPK1 kinase, in the case of Toll-like receptor 3/4 (TLR3/4), a RHIM-containing adaptor, called TRIF, while in the case of Z-DNA-binding protein ZBP1/DAI, the cytosolic viral sensor itself contains a RHIM domain. In this review, we discuss the different protein complexes that serve as nucleation platforms for necroptosis and the mechanism of execution of necroptosis. Transgenic models (knockout, kinase-dead knock-in) and pharmacologic inhibition indicate that RIPK1, RIPK3 or MLKL are implicated in many inflammatory, degenerative and infectious diseases. However, the conclusion of necroptosis being solely involved in the etiology of diseases is blurred by the pleiotropic roles of RIPK1 and RIPK3 in other cellular processes such as apoptosis and inflammasome activation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In particular, the activation of RIPK3 downstream of TNFR1 ligation relies on the formation of a RIPK1-containing and RIPK3-containing amyloid-like signaling complex commonly known as necrosome [436, 470], wherein first RIPK1 and then RIPK3 undergo a series of trans-phosphorylation or auto-phosphorylation events that are required for MLKL recruitment and necroptosis activation [437, 438, 442, 471]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [470]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
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
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X. (1996) · Cell · doi:10.1016/s0092-8674(00)80085-9 · Cited by 5,167
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
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Micheau, O., & Tschopp, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00521-x · Cited by 2,738
Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.031 · Cited by 2,698
Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion
He, W.-T., Wan, H., Hu, L., Chen, P., Wang, X., Huang, Z., Yang, Z.-H., Zhong, C.-Q., & Han, J. (2015) · Cell Research · doi:10.1038/cr.2015.139 · Cited by 2,517
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435
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
Self-citation
Cited by
Sorted by citations
Items 401–500 of 571
Identification of necroptosis-related gene signatures for predicting the prognosis of ovarian cancer
Qin, Y., Sheng, Y., Ren, M., Hou, Z., Xiao, L., & Chen, R. (2024) · Scientific Reports · doi:10.1038/s41598-024-61849-y · Cited by 7
“Necroptosis is dependent on receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain like pseudokinase (MLKL) from a morphological standpoint 6,7 .”
BackgroundNecroptosis in obesity: a complex cell death event
Liu, Z., Wang, S., Wang, W., Lv, R., & Sun, C. (2024) · APOPTOSIS · doi:10.1007/s10495-024-02055-z · Cited by 7
“During necrosome formation, phosphorylated RIPK3 recognises and phosphorylates PsKD, leading to the release of 4HB ([59, 60], oligomerisation of activated MLKL and interaction with negatively charged phosphatidylinositol phosphates or cardiolipin in the plasma membrane via positively charged…”
He, A., Huang, Z., Wang, J., Lu, H., Zhang, R., Wu, L., & Feng, Q. (2022) · Disease Markers · doi:10.1155/2022/3968303 · Cited by 6
“Furthermore, TNF signaling pathway was found to regulate the balance between cell survival and necroptosis [29].”
BackgroundXu, Y., Wu, Q., Tang, Z., Tan, Z., Pu, D., Tan, W., Zhang, W., & Liu, S. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm13010044 · Cited by 6
“They believed that apoptosis was a regulated cell death method, and that necrosis was an unregulated way of cell death [4].”
BackgroundRecent Progress in Small-Molecule Inhibitors for Critical Therapeutic Targets of Necroptosis
Fang, Z., Wei, H., Gou, W., Chen, L., Bi, C., Hou, W., & Li, Y. (2021) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0386 · Cited by 6
The origin and evolution of necroptosis signaling pathway in metazoa
Sun, J., Chang, R., & Song, L. (2025) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2025.105339 · Cited by 5
Quinazoline-2,4(1H,3H)-dione modulates STAT3 and FOXO3a signaling in HepG2 cells
Manoharan, S., Murugesan, K., Gunasekaran, S., Vedagiri, H., & Perumal, E. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108304 · Cited by 6
Heat shock proteins in cerebral ischemia-reperfusion injury: Mechanisms and therapeutic implications
Zhao, A., Zhang, G., Wei, H., Xu, Y., Gan, J., & Jiang, X. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115284 · Cited by 6
Molecular Cell Biology of Apoptosis in Health and Disease
Ahmed, A. S., & Tait, S. W. G. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-92785-0_1 · Cited by 6
“Once phosphorylated, MLKL permeabilises the plasma membrane leading to necroptotic cell death (Grootjans et al., 2017, Weinlich and Green, 2014) (Figure 2) .”
Mammalian innate antiviral defenses: beyond interferon
Rex, E. A., Shaffer, J., Deng, D. M., & Gammon, D. B. (2025) · Journal of Virology · doi:10.1128/jvi.01707-24 · Cited by 7
“Necroptosis is a caspase-independent, pro-inflammatory cell death program that morphologically resembles pyroptosis and serves as a fail-safe when apoptotic caspase activation is inhibited during infection (409–411).”
Le, T.-K., Kuo, C., Wu, C.-C., Chen, Y., & Hsieh, S.-L. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117618 · Cited by 5
Liu, P., Zhu, T., Guo, H., Lu-fan, Y., ZHANG, K.-C., Guo, X.-H., Zheng, C.-X., Lin, J., Wang, M.-Y., Fu, Y., et al. (2026) · Dental Research · doi:10.1016/j.dtrs.2026.100031 · Cited by 5
Ma, S., Sun, C., Wang, Y., Zhang, X., & Kuang, H. (2026) · Journal of Ovarian Research · doi:10.1186/s13048-026-02054-5 · Cited by 5
“In the context of PCOS, this necroptotic cascade not only triggers localized immune responses but also promotes fibroblast activation and abnormal extracellular matrix (ECM) deposition, which are fundamental to ovarian fibrosis and follicular arrest [39, 40].”
Cathepsin B induces kidney diseases through different types of programmed cell death
Zhao, Y., Zhuang, Y., Shi, J., Fan, H., Lv, Q., & Guo, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1535313 · Cited by 6
Oligomerised RIPK1 is the main core component of the CD95 necrosome
Ivanisenko, N. V., König, C., Hillert-Richter, L. K., Feoktistova, M., Pietkiewicz, S., Richter, M., Panayotova‐Dimitrova, D., Kaehne, T., & Lavrik, I. N. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00433-0 · Cited by 5
“Please include in your resubmission a detailed point-by-point response addressing all referees' comments.”
The Viral Knock: Ameliorating Cancer Treatment with Oncolytic Newcastle Disease Virus
Pathak, U., Pal, R. B., & Malik, N. (2023) · Life · doi:10.3390/life13081626 · Cited by 5
Shimizu, M., Ohwada, W., Yano, T., Kouzu, H., Sato, T., Ogawa, T., Osanami, A., Toda, Y., Nagahama, H., Tanno, M., et al. (2024) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2024.06.005 · Cited by 5
Weiss, A. M., López, M. A., Rosenberger, M. G., Kim, J. Y., Shen, J., Chen, Q., Ung, T. W.-M., Ibeh, U., Knight, H. R., Rutledge, N. S., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00516 · Cited by 4
Khan, M. B., Huang, X., Ye, X., Zhang, D., Wang, B., Xu, A., Li, R., Ren, A., Chen, C., Song, J., et al. (2024) · Annals of Medicine · doi:10.1080/07853890.2024.2405079 · Cited by 8
Uncovering Human Mixed Lineage Kinase Domain-Like Activation in Necroptosis
Guibao, C. D., Petrinjak, K., & Moldoveanu, T. (2019) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0229 · Cited by 5
The Microenvironment of Tongue Cancer
Tao, W., Li-Juan, Z., Li, K., Jing-yuan, L., Liu, X., & Liang, Y. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-59038-3_4 · Cited by 5
Pissas, K., Schilling, M., Tian, Y., & Gründer, S. (2023) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-023-02839-3 · Cited by 5
Сell death and its significance in reproductive pathology
Zhelavskyi, M. M., Kernychnyi, S., & Dmytriv, O. Y. (2021) · Ukrainian Journal of Veterinary and Agricultural Sciences · doi:10.32718/ujvas4-2.04 · Cited by 5
“It was found that mitoptosis takes place during cell differentiation, self-maintenance of hematopoietic stem cells, metabolic remodelling, and elimination of the paternal mitochondria in organisms with the maternal inheritance of the mitochondrial DNA (Swerdlow & Wilkins, 2020).”
BackgroundInfluentialp53 controls choice between apoptotic and non-apoptotic death following DNA damagePreprint
Honeywell, M. E., Isidor, M. S., Harper, N. W., Fontana, R. E., Cruz‐Gordillo, P., Porto, S. A., Fraser, C. S., Sarosiek, K. A., Guertin, D. A., Spinelli, J. B., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.17.524444 · Cited by 6
Tokgozoglu, J., Pistorio, V., Minini, M., Soret, P., Steunou, V., Delaunay, J.-L., Castel, J., Luquet, S. H., Nemazanyy, I., Beaupère, C., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08004-1 · Cited by 4
“Phosphorylated MLKL then oligomerizes and translocates to the plasma membrane, where it disrupts membrane integrity and triggers lytic cell death [6].”
Converging Molecular Mechanisms of Nucleated Cell Death Pathways and Procoagulant Platelet Formation
Li, C., Braun, A., Zu, J., Gudermann, T. W., Mammadova‐Bach, E., & Anders, H. (2025) · Cells · doi:10.3390/cells14141075 · Cited by 4
“In nucleated cells, necroptosis plays a key role in immune defense, inflammation, and cancer, combining features of apoptosis and necrosis [49].”
InfluentialМаслов, Л. Н., Воронков, Н. С., Sementsov, A. S., Джаги, А. С., Петроцеллис, Л. Д., Ванг, Х., Нестеров, Е. А., & Лишманов, Ю. Б. (2018) · Российский физиологический журнал им И М Сеченова · doi:10.7868/s0869813918070018 · Cited by 3
Cai, F., Wang, J., Wu, Y., Hu, Y., & Wang, Q. (2020) · Medical Science Monitor · doi:10.12659/msm.924242 · Cited by 4
“The C-terminal domain activates the N-terminal helix bundle [18].”
BackgroundWang, F., Xie, M., Chen, P., Wang, D., & Yang, M. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/8212286 · Cited by 4
“RIP1 dimerization can phosphorylate RIP1, and phosphorylated RIP1 composes complex IIb with FADD and caspase-8 while RIP3 forms complex IIc [59, 60].”
MLKL, a new actor of UVB-induced apoptosis in human diploid dermal fibroblasts
Gary, A.-S., Amouret, S., Montoni, A., & Rochette, P. J. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02004-4 · Cited by 4
“RIPK3 complex formation, called necrosome, and RIPK3 phosphorylation induce the activation by phosphorylation of MLKL, the effector of necroptosis [21].”
BackgroundCell Death Mechanisms in Mycobacterium abscessus Infection: A Double-Edged Sword
Prata, R. B. D. S., & Pinheiro, R. O. (2025) · Pathogens · doi:10.3390/pathogens14040391 · Cited by 4
“Although traditionally viewed as a passive process, necrosis can also occur in a regulated manner via necroptosis, a programmed form of necrosis mediated by RIPK1, RIPK3, and MLKL, which together form the necrosome complex that disrupts membrane integrity and promotes cell lysis [64–67].”
HDAC3 inhibition mitigates acute kidney injury by alleviating RIPK1-mediated programmed necrosis
Chen, Q., Chen, Q., Xie, M., Xie, M., Chen, Y., Chen, Y., Shan, R.-R., Shan, R.-R., Liu, X., Yu, J.-T., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1546950 · Cited by 4
“Necroptosis is initiated by the formation of “ necrosomes ” , the oligomeric complexes comprising receptor-interacting kinase 1 (RIPK1) and RIPK3, with RIPK1 acting as a key initiator (Grootjans et al., 2017; Zhao et al., 2020).”
Insights into O-GlcNAcylation and programmed cell death in cancer
Yan, X., Ren, W., Zhu, Z., Li, S., Shi, R., Sun, K., Zhi, K., Gao, L., & Zheng, J. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1560491 · Cited by 4
“During necroptotic cell death, the formation of receptor-interacting protein kinases 1/3 (RIPK1/3) induces the phosphorylation of pseudo kinase mixed lineage kinase domain-like protein (MLKL), leading to cell membrane destruction (Cho et al., 2009; He et al., 2009; Grootjans et al., 2017).”
Necroptosis in chronic obstructive pulmonary disease, a smoking gun?
Pierotti, C. L., & Silke, J. (2022) · Immunology and Cell Biology · doi:10.1111/imcb.12515 · Cited by 4
“pseudokinase, mixed lineage kinase domain-like protein (MLKL).(4) Following autophosphorylation and activation of RIPK1 and RIPK3, RIPK3 phosphorylates MLKL, which switches MLKL into an active conformation”
BackgroundBayonets over bombs: RIPK3 and MLKL restrict Listeria without triggering necroptosis
Zhang, T., & Balachandran, S. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201905047 · Cited by 5
Byun, H., Kwon, S., Wagner, K., Shin, H., & Lim, H. J. (2021) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-021-00788-z · Cited by 4
Malhi, H., & Gores, G. J. (2020) · doi:10.1002/9781119436812.ch17 · Cited by 4
Zhong, C., Wang, S., Zhang, J., Zheng, Q., Lei, Y., Xu, Y., Ren, T., & Sun, R. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156786 · Cited by 3
RIPK3 regulates microglial polarization through the TLR4/MyD88 pathway in neuropathic pain
Sihan, E., Song, Q., Zhang, Z., & Liang, Y. (2025) · Molecular Pain · doi:10.1177/17448069251377861 · Cited by 3
“7,8 In neuropathic pain, this process contributes to neuroinflammation and exacerbates pain hypersensitivity.”
Dietary Polyphenols Curcumin and Resveratrol Exert Selective Anticancer Effects in Melanoma Cells
Cho, M. K., Lee, Y., Kim, K. D., Choi, M., Lee, S.-H., Choi, D., Nam, H.-S., & Lee, Y. (2026) · Nutrients · doi:10.3390/nu18030548 · Cited by 3
“Necroptosis is a regulated cell death program mediated by RIPK − MLKL signaling [31].”
Paidlewar, M., Kumari, S., Dhapola, R., Sharma, P., Vellingiri, B., Medhi, B., & HariKrishnaReddy, D. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.03.053 · Cited by 3
Synthetic RIG-I-Agonist RNA Induces Death of Hepatocellular Carcinoma Cells
Ulloa, B. S., Barber-Axthelm, I. M., Berube, B. J., Duthie, M. S., Reed, S., Savan, R., & Gale, M. (2025) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2024.0195 · Cited by 3
“Signaling in cells de fi cient of the death receptor adapter protein Fas-associated death domain (FADD) or caspase-8 leads to deubiquitination of the serine/threonine kinase, RIP1, and its recruitment to family member, RIP3, to form a “ necrosome ” complex (Grootjans et al., 2017; Yoon et al., 2017).”
Mahmoud, M. E., Tingley, D., Faizal, A., Ghaffar, A., Azhar, M., Salman, D., Isham, I. M., & Abdul-Careem, M. F. (2025) · Viruses · doi:10.3390/v17040503 · Cited by 3
“Furthermore, we investigated the effects of 24-h treatment with caspase inhibitors (1/4, 3, 8, 9, and pan-caspase) on cell viability, apoptosis, and necroptosis in mock-infected chicken macrophages cultured under 4.5% serum conditions (Figure S4).”
InfluentialSirwi, A., Rabie, M. A., Koshak, A. E., Albadawi, D. A. I., Halawany, A. M. E., Ibrahim, S. R. M., Mohamed, G. A., Abdallah, H. M., & Sayed, N. S. E. (2025) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-025-00831-5 · Cited by 3
“Activated RIP1 and RIP3 forms a complex, named necrosome, which stimulates/ phosphorylates MLKL protein, a RIP3 substrate and a principal downstream effector of necroptosis [51].”
Land, W. G. (2018) · Springer eBooks · doi:10.1007/978-3-319-78655-1_19 · Cited by 3
“[7] , "a working model on the interaction between RIPK1 and RIPK3 emerges where inactive RIPK1 initially exists in a closed conformation at the TNFR1, where its DD and RHIM are unavailable for the formation of pro-cell death complexes.”
BackgroundMethodInfluentialSun, L., Li, W., Zhao, Z., Zuo, Y., & Han, Z. (2023) · International Journal of Genomics · doi:10.1155/2023/8766311 · Cited by 3
“Interestingly, TNF was referred as a key mediator in balancing cell survival and necroptosis [39].”
Reduction of ovarian reserves and activation of necroptosis to in vivo air pollution exposures
Namvar, Z., Tehrani, F. R., Shahsavani, A., Khodagholi, F., Hashemi, S. S., Binayi, F., Salimi, M., Abdollahifar, M., Hopke, P. K., & Mohseni-Bandpei, A. (2023) · International Journal of Environmental Health Research · doi:10.1080/09603123.2023.2210109 · Cited by 3
“The receptor systems lead to cell death through activation of RIPK3 and MLKL proteins (Grootjans et al. 2017; Zhang et al. 2020).”
BackgroundEşrefoğlu, M., Kalkan, T. K., Karataş, E., Elibol, B., Hekimoğlu, E. R., Cimen, F. B. K., & Arzu Hanım, Y. A. Y. (2023) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2023.2291751 · Cited by 3
“A type of programmed cell death known as necroptosis takes place after the receptor-interacting protein kinases RIPK1 and RIPK3 form an oligomeric complex known as the ‘necrosome’ [27].”
BackgroundKrishnasamy, N., Ramadoss, R., Selvam, S. P., Sundar, S., & Hema Shree, K. (2024) · Oral Oncology Reports · doi:10.1016/j.oor.2024.100378 · Cited by 3
Necrostatin‐1 attenuates oral squamous cell carcinoma by modulating tumour immune response in mice
Saravanan, L., Mahale, A. B., Gota, V., Khandelia, P., & Kulkarni, O. P. (2025) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.70008 · Cited by 3
“Activation of pattern recognition receptors (PRR) such as toll-like receptor 3 (TLR3), TLR4, Z-DNA binding protein 1 (ZBP1) and TNF-α receptor R1 are known to trigger necroptosis in cancer cells [3 – 7].”
Lecoeur, H., Zhang, S., Varet, H., Legendre, R., Proux, C., Granjean, C., Bousso, P., Prina, E., & Späth, G. F. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.14.507851 · Cited by 4
“In contrast, necroptosis and pyroptosis are two regulated necrotic (i.e. lytic) processes that have been associated to potent inflammatory responses in vivo (Bergsbaken et al., 2009; Frank and Vince, 2019; Grootjans et al., 2017; Pasparakis and Vandenabeele, 2015).”
BackgroundHost Cell Death Signaling Pathways Manipulated by Mycobacterium tuberculosisPreprint
Ding, G., & Briken, V. (2026) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041824 · Cited by 4
Unveiling New Horizons: Estrogen as a Breakthrough Therapy for Sepsis
Haloho, A. B. (2025) · Journal of Cellular & Molecular Anesthesia · doi:10.5812/jcma-159284 · Cited by 2
Mythri, C., Jorvekar, S. B., Suraj, N., Pruthiviraj, N., Borkar, R. M., & Selvaraju, S. (2025) · Molecular Omics · doi:10.1039/d5mo00039d · Cited by 2
Small molecules targeting regulated cell death for chronic kidney disease therapy
Yu, W.-K., Zhu, Q.-R., Zhou, L., Shen, X.-L., Cheng, T.-Y., Bao, Y., & Cao, G. (2025) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2025.101427 · Cited by 2
“Necroptosis is typically initiated by signals from TNF receptor 1 (TNFR1), Toll-like receptors (TLRs), and interferon (IFN) receptors (IFNRs), which recruit RIPK1/RIPK3 to trigger the pathway [93].”
Chen, Y.-Q., Zhang, J.-J., Guo, X.-F., Chen, Y.-K., Zhang, Q.-Y., Wang, Q., & Xie, X. (2025) · Food and Chemical Toxicology · doi:10.1016/j.fct.2025.115731 · Cited by 2
Liu, T., Liu, H., Chang, Y., Xu, S., & Xu, C. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.139872 · Cited by 2
Pan, P., Zhao, T., Zhang, J., Zhou, Y., Zhang, X., Li, Q., & Zhou, Y. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1605214 · Cited by 2
“Since the concept of PCD was proposed in the 20th century, apoptosis has been regarded as the main form of PCD, and it is generally believed that it is closely related to the activation of Caspase family (Grootjans et al., 2017).”
The Interaction Between Ferroptosis and Necroptosis in Acute and Chronic Kidney Diseases
Song, C., Chen, F., Fang, Y., Ding, X., Han, Q., Duan, Y., Ren, Q., Zhang, D., & Zhu, H. (2026) · Journal of Inflammation Research · doi:10.2147/jir.s559198 · Cited by 2
“50 When the ubiquitination of RIPK1 is inhibited or the phosphorylation induced by cytotoxicity is inhibited, RIPK1, FADD, and caspase-8 assemble into complex IIb, mediating apoptosis.”
Fang, X., Fu, Y., Ma, Y., Li, B., Zhang, Z., Mo, T., Li, A., Xie, Y., & Fu, Q. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1744884 · Cited by 2
“Additionally, RIPK1 interacts with RIPK3 via its RHIM domain to form the necrosome, resulting in MLKL phosphorylation and necroptosis induction (Ying et al., 2021; Grootjans et al., 2017).”
Virulence of Pathogens and the Counteracting Responses of the Host
Land, W. G. (2023) · Springer eBooks · doi:10.1007/978-3-031-21776-0_3 · Cited by 4
Basic Trajectories in Autoimmunity
Land, W. G. (2023) · Springer eBooks · doi:10.1007/978-3-031-21776-0_6 · Cited by 2
Hong, M., Wu, X., He, P., Peng, R., Li, L., Wu, S., Zhao, J., Han, A., Zhang, Y., Han, J., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114966 · Cited by 2
Ars moriendi: Proteases as sculptors of cellular suicide
Heib, M., Weiß, J., Saggau, C., Hoyer, J., Chico, J. F., Voigt, S., & Adam, D. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119191 · Cited by 2
Wei, J., Hou, S., Li, M., Yao, X., Wang, L., Zheng, Z., Mo, H., Chen, Y., & Yuan, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.875264 · Cited by 2
“Necroptosis is characterized by loss of plasma membrane integrity, swelling and deformation of cells and organelles, release of cellular contents, and further triggering inflammation to expand tissue damage (3, 4).”
BackgroundWu, Z., Fan, H., Qin, L., Niu, X., Chu, B., Zhang, K., Gao, Y., & Wang, H. (2025) · Journal of Molecular Neuroscience · doi:10.1007/s12031-024-02241-3 · Cited by 2
“Ultimately, MLKL is phosphorylated and polymerized, leading to the induction of necroptosis (Grootjans et al. 2017).”
Salvadores, N., Moreno‐González, I., Gamez, N., Quiroz, G., Vegas, L., Escandón, M., Jiménez, S., Vitórica, J., Gutiérrez, A., Soto, C. A., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.27.457960 · Cited by 2
Ildefonso, G. V., Metzig, M. O., Hoffmann, A., Harris, L. A., & Lopez, C. F. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.25.481705 · Cited by 2
RIPK3 coordinates RHIM domain-dependent inflammatory transcription in neuronsPreprint
Kofman, S. B., Chu, L. H., Ames, J. M., Chavarria, S. D., Lichauco, K., Daniels, B. P., & Oberst, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.29.582857 · Cited by 2
A Novel Class of RIP1/RIP3 Dual Inhibitors
Zhou, T., & Liu, B. (2020) · Journal of Cellular Immunology · doi:10.33696/2689-2812.2.013 · Cited by 1
Emerging treatments in graft reconditioning beyond machine perfusion
Luijmes, S. H., Broere, R., & de Jonge, J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99655-6.00005-1 · Cited by 1
Kishita, S., Umemura, N., Miyazaki, H., Adachi, M., Yagi, H., & Ohkoshi, E. (2025) · Oncology Reports · doi:10.3892/or.2025.8996 · Cited by 2
Infectious/Inflammatory Oral Diseases and Medication-Related Osteonecrosis of the Jaw (MRONJ)
Cintra, L. T. Â., Faverani, L. P., Wajima, C. S., Pereira, E. L., Toro, L. F., de Mello‐Neto, J. M., Neto, T. J. D. L., & Ervolino, E. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-03176-1_20 · Cited by 1
The Role of Short-Chain Fatty Acids Produced by Oral Bacteria in Modulating Oral Immunity
Tsuda, H., & Mikami, Y. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-03176-1_4 · Cited by 1
Ferroptosis Profiles of Human Mesenchymal Stromal Cell Subsets at the Single-Cell Level
Wen, X., Ding, S., Zhou, Y., Liu, S., Chen, H., & Sun, L. (2025) · DNA and Cell Biology · doi:10.1177/10445498251397930 · Cited by 1
Toro, L. F., Souza, E. Q. M., Ganzaroli, V. F., Freire, J. D. O. A., da Costa, L. L., Pereira, E. L., Machado, B. A., de Mello‐Neto, J. M., Matsumoto, M. A., Casatti, C. A., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27031355 · Cited by 1
“Various stimuli and chemical agents can trigger necroptosis in osteocytes, including inflammatory cytokines, damaged DNA, lipopolysaccharides (LPS), and pathogen-associated molecular patterns (PAMPs) [52,54].”
Tian, X., Jin, X., & Jiang, S. (2026) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2026.105574 · Cited by 1
Suptela, A. J., & Marriott, I. (2026) · Journal of NeuroVirology · doi:10.1007/s13365-025-01304-4 · Cited by 1
“Prior studies have indicated that caspase-8 can act as a negative regulator of RIPK1 mediated necrop-tosis via the interaction of the RHIM domains of RIPK1 and RIPK3 (Silke et al. 2015; Pasparakis and Vandenabeele 2015; Weinlich et al. 2017; Grootjans et al. 2017).”
Clark, C. J., Waddell, S., Tessmer, G. E., Womack, C. B., Xie, Y., Williams, B. D., Endraws, M. A., Huddleston, C. T., Pulis, K. D., Thammathong, J., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c02226 · Cited by 1
Targeting TNBC : core–shell polycationic polyurea dendrimers with inherent anticancer activity
Cruz, A., Abreu, B., Mendes, C., Freitas-Dias, C., Gonçalves, F., Silva, F. P., Ramalho, J. C., André, S., Bonifácio, V. D. B., & Serpa, J. (2026) · FEBS Open Bio · doi:10.1002/2211-5463.70144 · Cited by 1
“1 of TNF α , which can trigger cleaved caspase-3 (32) and activate p-RIP3 [35].”
Wang, L., Fang, D.-M., Jiang, Y., Jiang, X.-L., Ming-kui, W., & Shen, X. (2026) · Phytochemistry · doi:10.1016/j.phytochem.2026.114881 · Cited by 1
Focus on necroptosis: its role in the pathogenesis and therapeutic potential of osteoarthritis
Ouyang, Y., Liao, H., Kang, W., Li, F., & Shen, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1695254 · Cited by 1
“…speci fi c circumstances, such as the inhibition of the apoptotic pathway, that RIPK1 transitions to activate the necroptosis signaling pathway, illustrating its complex regulatory mechanism and establishing RIPK1 as a crucial “ molecular switch ” in determining cellular survival or death (47, 48).”
Yarmohammadi, F., Miraghaee, S., & Karimi, G. (2026) · Phytotherapy Research · doi:10.1002/ptr.70378 · Cited by 1
“Necroptosis is a regulated form of cell death that causes inflammation by releasing cellular contents (Grootjans et al. 2017).”
Exploring the intricate relationship between IL-1β and IL-18 in the context of osteoarthritis
Kumari, A., & Rasool, M. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1870390 · Cited by 1
Identification of necroptosis-related genes as prognostic indicators for lower-grade glioma.
Huang, X., Vafaei, S., Li, L., Wang, Y., Sun, J. L., Gao, Y., & Zhang, J. (2023) · PubMed Central · Cited by 1
Effect of Sublethal Concentrations of Metal Nanomaterials on Cell Energy Metabolism
Liang, C., Jiang, Q., Liu, Z., Yang, J. M., Zhang, J., Zhang, S., & Xin, W. (2023) · Toxics · doi:10.3390/toxics11050453 · Cited by 2
Ebola Virus Infection Induces HCAR2 Expression Leading to Cell Death
Kuroda, M., Halfmann, P., & Kawaoka, Y. (2023) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiad344 · Cited by 1
Programmed myofibre necrosis in critical illness acquired muscle wasting
Patel, S. K., Francis, T., Rajaram, R., Handslip, R., Mumby, S. E., Bear, D. E., Padhke, R., Hart, N., Montgomery, H., Takata, M., et al. (2023) · JCSM Rapid Communications · doi:10.1002/rco2.83 · Cited by 1
“5,11 A terminal step in this signalling pathway is the receptor interacting protein kinase 3 (RIPK3)-dependent phosphorylation of mixed-lineage kinase domain-like (pMLKL) protein.”
BackgroundExpression of RIPK3 among a cohort of Bulgarian patients with inflammatory bowel diseases
Panayotova, E., & Atanassova, A. (2022) · Varna Medical Forum · doi:10.14748/vmf.v0i0.8451 · Cited by 1
Guanine nucleotide exchange factor RABGEF1 facilitates TNF-induced necroptosis by targeting cIAP1
Chen, D., Chen, Y., Feng, J., Huang, W., Han, Z., Liu, Y., Lin, Q., Li, L., & Lin, Y. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149669 · Cited by 1
The modulation of necroptosis and its therapeutic potentials
KIM, C. S. (2021) · Molecular & Cellular Toxicology · doi:10.1007/s13273-021-00129-6 · Cited by 1
Die eukaryotische Zelle und Modellorganismen
Graw, J. (2020) · Springer eBooks · doi:10.1007/978-3-662-60909-5_5 · Cited by 1
ZBP1-mediated macrophage necroptosis inhibits ASFV replicationPreprint
Zhang, K., Yu, H., Yang, B., Yang, J., Zhang, D., Yang, X., Shi, X., Zhao, D., Chen, L., Yan, W., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.25.538262 · Cited by 1
“Phosphorylated MLKL in 101 necrosome polymerizes on the cytoplasmic membrane, forming membrane pores and 102 driving plasma membrane leakage (19, 20).”
BackgroundGao, W., Gao, B., Wang, S., Wu, D., Mei, P., Geng, L., Li, C., Li, Y., Liu, X., Pan, J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.28.656730 · Cited by 1
“In addition, RIPK1 also has a death domain (DD) at its C terminus for recruitment to the TNF receptor signaling complex 21,22 (Fig.”
Pro-necroptotic agents in cancer therapy
Elsharkawy, A. M., & Malki, A. M. (2018) · Annals of Breast Cancer · doi:10.33582/2640-8198/1004
Nigratine as first-in-class dual inhibitor of necroptosis and ferroptosis regulated cell deathPreprint
Delehouzé, C., Comte, A., Hauteville, M., Goekjian, P. G., Dimanche‐Boitrel, M., Rousselot, M., & Bach, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.15.422885
The antipsychotic drug pimozide is a novel chemotherapeutic agent for adult T cell leukemiaPreprint
Ishikawa, C., & Mori, N. (2021) · Research Square · doi:10.21203/rs.3.rs-272455/v1
“Besides apoptosis, another mode of programmed cell death, necroptosis, has also been identi ed [9].”
BackgroundMechanisms of Cardiomyocyte Death
Kartha, C. C. (2021) · Springer eBooks · doi:10.1007/978-3-030-85536-9_13
Bigio, M. R. D. (2021) · Cambridge University Press eBooks · doi:10.1017/9781316671863.030
Xia, P., Wang, D., Shen, R., Guo, Z., Ouyang, S., Yang, X., Liu, X., & Xie, K. (2022) · Research Square · doi:10.21203/rs.3.rs-1601242/v1
Metadata
- Authors
- Grootjans, S., Vanden Berghe, T., & Vandenabeele, P.
- Affiliations
- Ghent University (BE)
- Corresponding author
- Vandenabeele, Peter
- Venue
- Cell Death & Differentiation
- Published
- 2017-05-12
- Volume
- 24
- Issue
- 7
- Pages
- 1184-1195
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC5520172
- OpenAlex
- W2612992363
- Cited by
- 566
- References
- 152
- Citations by year
- 2026: 45 · 2025: 66 · 2024: 68 · 2023: 78 · 2022: 89 · 2021: 64 · 2020: 54 · 2019: 47 · 2018: 41 · 2017: 14
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Belgian Federal Science Policy Office (IAP7/32)
- Fonds Wetenschappelijk Onderzoek (G.0875.11, FWO G.0A45.12N, FWO G0E04.16N, G078713N, FWO G0787.13N, FWO G.0C37.14N, G0C3714N, G.0A45.12N, FWO G.0875.11, BOF16/MET_V/007, G0E0416N)
- Universiteit Gent (BOF16/MET_V/007, 01M00709)
- Vlaams Instituut voor Biotechnologie (BOF09/01M00709)
- Vlaamse regering (BOF09/01M00709, BOF16/MET_V/007)
- Fondation contre le Cancer (2012-188)
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- necroptosis, regulated cell death, RIPK3, RIPK1, MLKL, RHIM domain, Toll-like receptors, TRIF, ZBP1, DAI, pattern recognition receptors, inflammatory diseases, degenerative diseases, infectious diseases, apoptosis, inflammasome activation
- MeSH terms
- Amyloid, Animals, Humans, Models, Biological, Necrosis, Signal Transduction, Apoptosis, Receptor-Interacting Protein Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
