NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria
Open accessAbstract
Nuclear factor κB (NF-κB), a key activator of inflammation, primes the NLRP3-inflammasome for activation by inducing pro-IL-1β and NLRP3 expression. NF-κB, however, also prevents excessive inflammation and restrains NLRP3-inflammasome activation through a poorly defined mechanism. We now show that NF-κB exerts its anti-inflammatory activity by inducing delayed accumulation of the autophagy receptor p62/SQSTM1. External NLRP3-activating stimuli trigger a form of mitochondrial (mt) damage that is caspase-1- and NLRP3-independent and causes release of direct NLRP3-inflammasome activators, including mtDNA and mtROS. Damaged mitochondria undergo Parkin-dependent ubiquitin conjugation and are specifically recognized by p62, which induces their mitophagic clearance. Macrophage-specific p62 ablation causes pronounced accumulation of damaged mitochondria and excessive IL-1β-dependent inflammation, enhancing macrophage death. Therefore, the "NF-κB-p62-mitophagy" pathway is a macrophage-intrinsic regulatory loop through which NF-κB restrains its own inflammation-promoting activity and orchestrates a self-limiting host response that maintains homeostasis and favors tissue repair.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Multiple components of molecular machinery for necroptosis-including ZBP1, RIPK3, MLKL, and TNFR1 (mainly via NF-κB)-impinge on control of inflammasome, a supramolecular platform for activation of CASP1 and consequent secretion of mature IL1B and IL18.
“Importantly, multiple components of the molecular machinery for necroptosis—including ZBP1, RIPK3, MLKL, and TNFR1 (mainly via NF-κB)—impinge on the control of the so-called “inflammasome”, a supramolecular platform for the activation of CASP1 and consequent secretion of mature interleukin 1 beta (IL1B; best known as IL-1β) and IL18 [524–529].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [528]
Cites
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618 · see citing works
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602 · see citing works
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475 · see citing works
Nuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases
Barnes, P. J., & Karin, M. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704103361506 · Cited by 4,622 · see citing works
Self-citationAutophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,441 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065 · see citing works
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049 · see citing works
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835 · see citing works
The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
Lazarou, M., Sliter, D. A., Kane, L. A., Sarraf, S. A., Wang, C., Burman, J. L., Sideris, D. P., Fogel, A. I., & Youle, R. J. (2015) · Nature · doi:10.1038/nature14893 · Cited by 2,774 · see citing works
Regulation and Function of NF-κB Transcription Factors in the Immune System
Vallabhapurapu, S., & Karin, M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132641 · Cited by 2,578 · see citing works
Self-citationMechanisms and Functions of Inflammasomes
Lamkanfi, M., & Dixit, V. M. (2014) · Cell · doi:10.1016/j.cell.2014.04.007 · Cited by 2,521 · see citing works
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., et al. (2012) · Nature · doi:10.1038/nature10809 · Cited by 2,435 · see citing works
Self-citationImpairment of starvation-induced and constitutive autophagy in <i>Atg7</i> -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331 · see citing works
The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310 · see citing works
Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis
Shimada, K., Crother, T. R., Karlin, J., Dagvadorj, J., Chiba, N., Chen, S., Ramanujan, V. K., Wolf, A. J., Vergnes, L., Ojcius, D. M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.009 · Cited by 2,282 · see citing works
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124 · see citing works
Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production
Saitoh, T., Fujita, N., Jang, M. H., Uematsu, S., Yang, B., Satoh, T., Omori, H., Noda, T., Yamamoto, N., Komatsu, M., et al. (2008) · Nature · doi:10.1038/nature07383 · Cited by 2,020 · see citing works
Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
Eisenbarth, S. C., Colegio, O. R., O’Connor, W., Sutterwala, F. S., & Flavell, R. A. (2008) · Nature · doi:10.1038/nature06939 · Cited by 1,542 · see citing works
Shi, C.-S., Shenderov, K., Huang, N.-N., Kabat, J., Abu-Asab, M., Fitzgerald, K. A., Sher, A., & Kehrl, J. H. (2012) · Nature Immunology · doi:10.1038/ni.2215 · Cited by 1,367 · see citing works
Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes
Lu, A., Magupalli, V. G., Ruan, J., Yin, Q., Atianand, M. K., Vos, M. R., Schröder, G. F., Fitzgerald, K. A., Wu, H., & Egelman, E. H. (2014) · Cell · doi:10.1016/j.cell.2014.02.008 · Cited by 1,353 · see citing works
Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
Miao, E. A., Leaf, I. A., Treuting, P. M., Mao, D. P., Dors, M., Sarkar, A., Warren, S. E., Wewers, M. D., & Aderem, A. (2010) · Nature Immunology · doi:10.1038/ni.1960 · Cited by 1,336 · see citing works
Homeostasis, Inflammation, and Disease Susceptibility
Kotas, M. E., & Medzhitov, R. (2015) · Cell · doi:10.1016/j.cell.2015.02.010 · Cited by 1,213 · see citing works
Molecular inflammation: Underpinnings of aging and age-related diseases
Chung, H. Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A. Y., Carter, C., Yu, B. P., & Leeuwenburgh, C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2008.07.002 · Cited by 1,203 · see citing works
Intracellular pattern recognition receptors in the host response
Meylan, E., Tschopp, J., & Karin, M. (2006) · Nature · doi:10.1038/nature04946 · Cited by 1,196 · see citing works
Self-citationp62 at the crossroads of autophagy, apoptosis, and cancer
Moscat, J., & Diaz-Meco, M. T. (2009) · Cell · doi:10.1016/j.cell.2009.05.023 · Cited by 1,073 · see citing works
Self-citationDecoding cell death signals in liver inflammation
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.033 · Cited by 1,022 · see citing works
Hepatic inflammation and fibrosis: Functional links and key pathways
Seki, E., & Schwabe, R. F. (2015) · Hepatology · doi:10.1002/hep.27332 · Cited by 972 · see citing works
Self-citationInflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935 · see citing works
Initiation and perpetuation of <scp>NLRP</scp> 3 inflammasome activation and assembly
Elliott, E. I., & Sutterwala, F. S. (2015) · Immunological Reviews · doi:10.1111/imr.12286 · Cited by 821 · see citing works
Baroja-Mazo, A., Martín-Sánchez, F., Gomez, A. I., Martínez, C. M., Amores-Iniesta, J., Compan, V., Barberà-Cremades, M., Yagüe, J., Ruiz-Ortiz, E., Antón, J., et al. (2014) · Nature Immunology · doi:10.1038/ni.2919 · Cited by 790 · see citing works
Narendra, D. P., Kane, L. A., Hauser, D. N., Fearnley, I. M., & Youle, R. J. (2010) · Autophagy · doi:10.4161/auto.6.8.13426 · Cited by 789 · see citing works
The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation
Franklin, B. S., Bossaller, L., De Nardo, D., Ratter, J. M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S. R., Al-Amoudi, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2913 · Cited by 773 · see citing works
A gp130–Src–YAP module links inflammation to epithelial regeneration
Taniguchi, K., Wu, L.-W., Grivennikov, S. I., de Jong, P. R., Lian, I., Yu, F.-X., Wang, K., Ho, S. B., Boland, B. S., Chang, J. T., et al. (2015) · Nature · doi:10.1038/nature14228 · Cited by 633 · see citing works
Self-citationGreten, F. R., Arkan, M. C., Bollrath, J., Hsu, L.-C., Goode, J., Miething, C., Göktuna, S. I., Neuenhahn, M., Fierer, J., Paxian, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.009 · Cited by 616 · see citing works
Self-citationPINK1/Parkin-mediated mitophagy in mammalian cells
Eiyama, A., & Okamoto, K. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.01.002 · Cited by 603 · see citing works
DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.036 · Cited by 592 · see citing works
The ubiquitin ligase parkin mediates resistance to intracellular pathogens
Manzanillo, P. S., Ayres, J. S., Watson, R. O., Collins, A. C., Souza, G., Rae, C. S., Schneider, D. S., Nakamura, K., Shiloh, M. U., & Cox, J. S. (2013) · Nature · doi:10.1038/nature12566 · Cited by 588 · see citing works
Innate immunity and inflammation in ageing: a key for understanding age-related diseases
Licastro, F., Candore, G., Lio, D., Porcellini, E., Colonna-Romano, G., Franceschi, C., & Caruso, C. (2005) · Immunity & Ageing · doi:10.1186/1742-4933-2-8 · Cited by 453 · see citing works
Inflammasome activation leads to Caspase-1–dependent mitochondrial damage and block of mitophagy
Yu, J.-J., Nagasu, H., Murakami, T., Hoang, H., Broderick, L., Hoffman, H., & Horng, T. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1414859111 · Cited by 449 · see citing works
Self-citationRecognition of Bacteria by Inflammasomes
von Moltke, J., Ayres, J. S., Kofoed, E. M., Chavarría‐Smith, J., & Vance, R. E. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095944 · Cited by 414 · see citing works
p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria
Okatsu, K., Saisho, K., Shimanuki, M., Nakada, K., Shitara, H., Sou, Y., Kimura, M., Sato, S., Hattori, N., Komatsu, M., et al. (2010) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01426.x · Cited by 397 · see citing works
TRPM2 links oxidative stress to NLRP3 inflammasome activation
Zhong, Z., Zhai, Y., Liang, S., Mori, Y., Han, R., Sutterwala, F. S., & Qiao, L. (2013) · Nature Communications · doi:10.1038/ncomms2608 · Cited by 374 · see citing works
Self-citationp62/SQSTM1/A170: Physiology and pathology
Komatsu, M., Kageyama, S., & Ichimura, Y. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.07.004 · Cited by 301 · see citing works
The IKK complex contributes to the induction of autophagy
Criollo, A., Senovilla, L., Authier, H., Maiuri, M. C., Morselli, E., Vitale, I., Kepp, O., Tasdemir, E., Galluzzi, L., Shen, S., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.364 · Cited by 296 · see citing works
Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62
Rodriguez, A., Durán, A., Selloum, M., Champy, M.-F., Diez-Guerra, F. J., Flores, J. M., Serrano, M., Auwerx, J., Diaz-Meco, M. T., & Moscat, J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.011 · Cited by 290 · see citing works
Self-citationDivergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies
Brydges, S. D., Broderick, L., McGeough, M. D., Peña, C. A., Mueller, J. L., & Hoffman, H. M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci71543 · Cited by 228 · see citing works
Self-citationVance, R. E. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.01.010 · Cited by 210 · see citing works
Single-Cell Imaging of Caspase-1 Dynamics Reveals an All-or-None Inflammasome Signaling Response
Liu, T., Yamaguchi, Y., Shirasaki, Y., Shikada, K., Yamagishi, M., Hoshino, K., Kaisho, T., Takemoto, K., Suzuki, T., Kuranaga, E., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.012 · Cited by 150 · see citing works
Kim, S., & Lee, S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.08.178 · Cited by 143 · see citing works
Vonlaufen, A., Xu, Z., Daniel, B., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.06.062 · Cited by 135 · see citing works
Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress
Chernyak, B. V., Izyumov, D. S., Lyamzaev, K. G., Pashkovskaya, A. A., Pletjushkina, O. Y., Antonenko, Y. N., Sakharov, D. V., WIRTZ, K. W. A., & Skulachev, V. P. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.02.019 · Cited by 129 · see citing works
Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice
Li, N., Wu, X., Holzer, R. G., Lee, J. H., Todoric, J., Park, E.-J., Ogata, H., Gukovskaya, A. S., Gukovsky, I., Pizzo, D. P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64498 · Cited by 124 · see citing works
Self-citationp62 Links β-adrenergic input to mitochondrial function and thermogenesis
Müller, T. D., Lee, S. J., Jastroch, M., Kabra, D. G., Stemmer, K., Aichler, M., Abplanalp, B., Ananthakrishnan, G., Bhardwaj, N. J., Collins, S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64209 · Cited by 122 · see citing works
Self-citationIL-1β-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKβ
Hsu, L.-C., Enzler, T., Seita, J., Timmer, A. M., Lee, C., Lai, T., Yu, G., Lai, L., Temkin, V., Sinzig, U., et al. (2010) · Nature Immunology · doi:10.1038/ni.1976 · Cited by 119 · see citing works
Self-citationKim, J. Y., & Ozato, K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802755 · Cited by 95 · see citing works
Stumptner, C., Fuchsbichler, A., Zatloukal, K., & Denk, H. (2007) · Hepatology · doi:10.1002/hep.21744 · Cited by 55 · see citing works
Chernyak, B. V., Izyumov, D. S., Lyamzaev, K. G., Pashkovskaya, A. A., Pletjushkina, O. Y., Antonenko, Y. N., Sakharov, D. V., WIRTZ, K. W. A., & Skulachev, V. P. (2006) · Acta Biochimica et Biophysica Sinica · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
NF-κB signaling in inflammation
Liu, T., Zhang, L., Joo, D., & Sun, S.-C. (2017) · Signal Transduction and Targeted Therapy · doi:10.1038/sigtrans.2017.23 · Cited by 8,791 · see citing works
Galluzzi, 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-citationNF-κB, inflammation, immunity and cancer: coming of age
Taniguchi, K., & Karin, M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.142 · Cited by 2,679 · see citing works
Self-citationRETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation
Sliter, D. A., Martinez, J., Hao, L., Chen, X., Sun, N., Fischer, T. D., Burman, J. L., Li, Y., Zhang, Z., Narendra, D. P., et al. (2018) · Nature · doi:10.1038/s41586-018-0448-9 · Cited by 1,287 · see citing works
RetractedAge and Age-Related Diseases: Role of Inflammation Triggers and Cytokines
Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00586 · Cited by 1,267 · see citing works
New mitochondrial DNA synthesis enables NLRP3 inflammasome activation
Zhong, Z., Liang, S., Sanchez-Lopez, E., He, F., Shalapour, S., Lin, X.-J., Wong, J., Ding, S., Seki, E., Schnabl, B., et al. (2018) · Nature · doi:10.1038/s41586-018-0372-z · Cited by 1,208 · see citing works
Self-citationMitochondrial DNA in innate immune responses and inflammatory pathology
West, A. P., & Shadel, G. S. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.21 · Cited by 1,115 · see citing works
Autophagy in inflammation, infection, and immunometabolism
Deretic, V. (2021) · Immunity · doi:10.1016/j.immuni.2021.01.018 · Cited by 862 · see citing works
Xian, H., Watari, K., Sanchez-Lopez, E., Offenberger, J., Onyuru, J., Sampath, H., Ying, W., Hoffman, H. M., Shadel, G. S., & Karin, M. (2022) · Immunity · doi:10.1016/j.immuni.2022.06.007 · Cited by 850 · see citing works
Self-citationLin, Q., Li, S., Jiang, N., Shao, X., Zhang, M., Jin, H., Zhang, Z., Shen, J., Zhou, Y., Zhou, W., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101254 · Cited by 632 · see citing works
Resolution of Inflammation: What Controls Its Onset?
Sugimoto, M. A., Sousa, L. P., Pinho, V., Perretti, M., & Teixeira, M. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00160 · Cited by 638 · see citing works
Autophagy balances inflammation in innate immunity
Deretic, V., & Levine, B. (2018) · Autophagy · doi:10.1080/15548627.2017.1402992 · Cited by 563 · see citing works
Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration
Choi, I., Zhang, Y., Seegobin, S. P., Pruvost, M., Wang, Q., Purtell, K., Zhang, B., & Yue, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-15119-w · Cited by 549 · see citing works
The role of mitochondria in NLRP3 inflammasome activation
Liu, Q., Zhang, D., Hu, D., Zhou, X., & Zhou, Y. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.09.010 · Cited by 475 · see citing works
Han, X., Sun, S., Sun, Y., Song, Q., Zhu, J., Song, N., Chen, M., Sun, T., Xia, M., Ding, J., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1596481 · Cited by 408 · see citing works
Autophagy and the cell biology of age-related disease
Leidal, A. M., Levine, B., & Debnath, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0235-8 · Cited by 424 · see citing works
Mechanisms of Selective Autophagy
Lamark, T., & Johansen, T. (2021) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120219-035530 · Cited by 429 · see citing works
Autophagy in liver diseases: Time for translation?
Allaire, M., Rautou, P.-E., Codogno, P., & Lotersztajn, S. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.01.026 · Cited by 378 · see citing works
Mitophagy: An Emerging Role in Aging and Age-Associated Diseases
Chen, G., Kroemer, G., & Kepp, O. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00200 · Cited by 359 · see citing works
The role of mitochondria in aging
Jang, J. Y., Blum, A., Liu, J., & Finkel, T. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120842 · Cited by 358 · see citing works
Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation
Dang, E. V., McDonald, J. G., Russell, D. W., & Cyster, J. G. (2017) · Cell · doi:10.1016/j.cell.2017.09.029 · Cited by 348 · see citing works
What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion?
Albensi, B. C. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00154 · Cited by 341 · see citing works
The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes
Sallman, D. A., & List, A. (2019) · Blood · doi:10.1182/blood-2018-10-844654 · Cited by 273 · see citing works
Mehto, S., Jena, K. K., Nath, P., Chauhan, S., Kolapalli, S. P., Das, S. K., Sahoo, P. K., Jain, A., Taylor, G. A., & Chauhan, S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.018 · Cited by 238 · see citing works
Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome
Su, H., Yang, F., Fu, R., Trinh, B., Sun, N., Liu, J., Kumar, A., Baglieri, J., Siruno, J., Le, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05169-z · Cited by 221 · see citing works
Self-citationDela Cruz, C. S., & Kang, M.-J. (2018) · Mitochondrion · doi:10.1016/j.mito.2017.12.001 · Cited by 255 · see citing works
Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
Li, Y., Xia, Y., Yin, S., Wan, F., Hu, J., Kou, L., Sun, Y., Wu, J., Zhou, Q., Huang, J., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.719807 · Cited by 230 · see citing works
Inflammasome and Autophagy Regulation: A Two-way Street
Sun, Q., Fan, J., Billiar, T. R., & Scott, M. J. (2017) · Molecular Medicine · doi:10.2119/molmed.2017.00077 · Cited by 203 · see citing works
Mishra, S. R., Mahapatra, K. K., Behera, B. P., Patra, S., Bhol, C. S., Panigrahi, D. P., Praharaj, P. P., Singh, A., Patil, S., Dhiman, R., et al. (2021) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2021.106013 · Cited by 195 · see citing works
Peng, X., Wang, Y., Li, H., Fan, J., Shen, J., Yu, X., Zhou, Y., & Mao, H. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1483-7 · Cited by 183 · see citing works
NF-κB: a double-edged sword controlling inflammation
Liu, D., Zhong, Z., & Karin, M. (2022) · Biomedicines · doi:10.3390/biomedicines10061250 · Cited by 157 · see citing works
Self-citationMouton‐Liger, F., Rosazza, T., Sepulveda‐Diaz, J., Ieang, A., Hassoun, S., Claire, E., Mangone, G., Brice, A., Michel, P. P., Corvol, J., et al. (2018) · Glia · doi:10.1002/glia.23337 · Cited by 160 · see citing works
Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation
Berglund, R., Guerreiro-Cacais, A. O., Adzemovic, M. Z., Zeitelhofer, M., Lund, H., Ewing, E., Ruhrmann, S., Nutma, E., Parsa, R., Thessen-Hedreul, M., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.abb5077 · Cited by 149 · see citing works
Defective autophagy in atherosclerosis: to die or to senesce?
Grootaert, M. O. J., Roth, L., Schrijvers, D. M., De Meyer, G. R. Y., & Martinet, W. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7687083 · Cited by 147 · see citing works
Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases
Corti, O., Blomgren, K., Poletti, A., & Beart, P. M. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15002 · Cited by 141 · see citing works
Mitochondria as a centrally positioned hub in the innate immune response
Sandhir, R., Halder, A., & Sunkaria, A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.10.020 · Cited by 135 · see citing works
Han, X., Zhu, J., Zhang, X., Song, Q., Ding, J., Lu, M., Sun, S., & Hu, G. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00397 · Cited by 91 · see citing works
Factors modulating the inflammatory response in acute gouty arthritis
Cleophas, M. C., Crişan, T. O., & Joosten, L. A. B. (2017) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000366 · Cited by 62 · see citing works
Inflammatory signaling in NASH driven by hepatocyte mitochondrial dysfunctions
Myint, M., Oppedisano, F., De Giorgi, V., Kim, B.-M., Marincola, F. M., Alter, H. J., & Nesci, S. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04627-0 · Cited by 61 · see citing works
Adlimoghaddam, A., Odero, G. G., Glazner, G., Turner, R. S., & Albensi, B. C. (2021) · Aging and disease · doi:10.14336/ad.2020.0910 · Cited by 38 · see citing works
He, W., Wei, J., Liu, X., Zhang, Z., Huang, R., & Jiang, Z. (2024) · Scientific Reports · doi:10.1038/s41598-024-62465-6 · Cited by 30 · see citing works
Cuadrado, A., Cazalla, E., Bach, A., Bathish, B., Naidu, S. D., DeNicola, G. M., Dinkova-Kostova, A. T., Fernández-Ginés, R., Grochot-Przeczek, A., Hayes, J. D., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103569 · Cited by 28 · see citing works
Manipulation of selective macroautophagy by pathogens at a glance
Cong, Y., Dinesh Kumar, N., Mauthe, M., Verlhac, P., & Reggiori, F. (2020) · Journal of Cell Science · doi:10.1242/jcs.240440 · Cited by 23 · see citing works
NLRP3 inflammasome: common nexus between depression and cardiovascular diseases
Alcocer-Gómez, E., & Cordero, M. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.214 · Cited by 20 · see citing works
- Authors
- Zhong, Z., Umemura, A., Sanchez-Lopez, E., Liang, S., Shalapour, S., Wong, J., He, F., Boassa, D., Perkins, G., Ali, S. R., McGeough, M. D., Ellisman, M. H., Seki, E., Gustafsson, A. B., Hoffman, H. M., Diaz-Meco, M. T., Moscat, J., & Karin, M.
- Affiliations
- University of California San Diego (US)
- Cedars-Sinai Medical Center (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Karin, Michael
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 164
- Issue
- 5
- Pages
- 896-910
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4769378
- OpenAlex
- W2275879522
- Cited by
- 1,197
- References
- 58
- Citations by year
- 2026: 110 · 2025: 123 · 2024: 119 · 2023: 119 · 2022: 144 · 2021: 136 · 2020: 132 · 2019: 110 · 2018: 88 · 2017: 79 · 2016: 35 · 2015: 1
- FWCI
- 54.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (135425_1)
- National Institute on Alcohol Abuse and Alcoholism (R01AA020172, AA020172)
- National Heart, Lung, and Blood Institute (HL087023, R01HL087023)
- National Cancer Institute (R01CA192642, R01CA163798, CA163798, R01CA132847, CA 030199, R01CA172025, CA132847, R01CA155120, P01CA128814, CA172025, CA192642, P30CA030199)
- National Institute of General Medical Sciences (P41GM103412, GM103412)
- National Institute of Allergy and Infectious Diseases (AI-043477, AI52430, R01AI043477, R01AI052430, R37AI043477)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK085252, R01DK085252, P01DK098108)
- National Institute of Environmental Health Sciences (P42ES010337, ES 010337)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- NF-κB, NLRP3 inflammasome, inflammasome activation, p62, mitophagy, mitochondrial damage, Parkin, ubiquitin conjugation, mitochondrial DNA, mitochondrial reactive oxygen species, IL-1β, macrophages, anti-inflammatory regulation, tissue repair
- MeSH terms
- Sequestosome-1 Protein, Animals, Heat-Shock Proteins, Lipopolysaccharides, Macrophages, Mitochondria, Reactive Oxygen Species, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Mice, NF-kappa B p50 Subunit, Interleukin-1beta, Inflammasomes
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
