Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome
Open accessAbstract
Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. Here we demonstrate that depletion of the autophagic proteins LC3B and beclin 1 enhanced the activation of caspase-1 and secretion of interleukin 1β (IL-1β) and IL-18. Depletion of autophagic proteins promoted the accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial reactive oxygen species (ROS). Cytosolic mtDNA contributed to the secretion of IL-1β and IL-18 in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity.
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
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?
Autophagy malfunction is related to presence of undegraded mtDNA recognized by TLR9 resulting in inflammation.
“Recent data have established a relationship between autophagy malfunction and presence of undegraded mtDNA, which is recognized by TLR9 and results in inflammation (Nakahira et al, 2011;Oka et al, 2012).”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as Nakahira et al, 2011
Autophagy malfunction causes mtDNA-mediated inflammation.
“Based on data indicating that autophagy malfunction caused mtDNA-mediated inflammation (Nakahira et al, 2011;Oka et al, 2012)”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as Nakahira et al, 2011
Cytosolic mtDNA can activate the NLRP3 inflammasome.
“mtDNA has been shown to activate the NLRP3 inflammasome.”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Nakahira et al., 2011
NLRP3 contributes to mtDNA release by facilitating mPTP formation in the mitochondrial inner membrane.
“The authors also suggested that as well as acting as a downstream sensor of cytoplasmic mtDNA, NLRP3 also contributes to mtDNA release by facilitating mPTP formation in the mitochondria inner membrane (Nakahira et al., 2011).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Nakahira et al., 2011
Treating cells with dysfunctional mitochondria with LPS or ATP increased cytosolic mtDNA, which contributed to IL-1β and IL-18 secretion via the NLRP3 inflammasome.
“One study showed that treating cells that have dysfunctional mitochondria with lipopolysaccharide (LPS) or ATP resulted in increased levels of cytosolic mtDNA, which contributed to secretion of IL-1β and IL-18 via the NLRP3 inflammasome (Nakahira et al., 2011).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Nakahira et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475 · see citing works
Circulating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812 · see citing works
Regulation mechanisms and signaling pathways of autophagy
He, C., & Klionsky, D. J. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102808-114910 · Cited by 3,609 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708 · see citing works
Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658 · cited 1× · see citing works
“Crystalline particles such as asbestos, silica and monosodium urate have been shown to activate the NALP3 inflammasome through ROS generation induced by phagocytic NADPH oxidas”
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311 · 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
Franchi, L., Eigenbrod, T., Muñoz-Planillo, R., & Nuñez, G. (2009) · Nature Immunology · doi:10.1038/ni.1703 · Cited by 1,834 · see citing works
Human Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by Complementation
King, M. P., & Attardi, G. M. (1989) · Science · doi:10.1126/science.2814477 · Cited by 1,659 · see citing works
Mitochondrial Respiratory-Chain Diseases
DiMauro, S., & Schon, E. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra022567 · Cited by 1,650 · see citing works
IFI16 is an innate immune sensor for intracellular DNA
Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., Sirois, C. M., Jin, T., Latz, E., Xiao, T. S., et al. (2010) · Nature Immunology · doi:10.1038/ni.1932 · Cited by 1,643 · see citing works
Self-citationLi, N., Ragheb, K., Lawler, G., Sturgis, J., Rajwa, B. P., Melendez, J. A., & Robinson, J. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210432200 · Cited by 1,434 · see citing works
Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C. G., McDowell, J., Paskind, M. P., Rodman, L., Salfeld, J. G., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90490-5 · Cited by 1,408 · see citing works
Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation
(1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90040-d · Cited by 1,386 · see citing works
The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
Rathinam, V. A. K., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., Vanaja, S. K., Monks, B. G., Ganesan, S., Latz, E., et al. (2010) · Nature Immunology · doi:10.1038/ni.1864 · Cited by 1,331 · see citing works
Self-citationSutterwala, F. S., Ogura, Y., Szczepanik, M., Lara-Tejero, M., Lichtenberger, G. S., Grant, E. P., Bertin, J., Coyle, A. J., Galán, J. E., Askenase, P. W., et al. (2006) · Immunity · doi:10.1016/j.immuni.2006.02.004 · Cited by 980 · see citing works
Mitochondrial Dynamics in Mammalian Health and Disease
Liesa, M., Palacín, M., & Zorzano, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00030.2008 · Cited by 953 · see citing works
Glyburide inhibits the Cryopyrin/Nalp3 inflammasome
Lamkanfi, M., Mueller, J. L., Vitari, A. C., Misaghi, S., Fedorova, A., Deshayes, K., Lee, W. P., Hoffman, H. M., & Dixit, V. M. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200903124 · Cited by 820 · see citing works
Cruz, C. M., Rinna, A., Forman, H. J., Ventura, A. L. M., Persechini, P. M., & Ojcius, D. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608083200 · Cited by 786 · see citing works
The AIM2 inflammasome is critical for innate immunity to Francisella tularensis
Fernandes-Alnemri, T., Yu, J.-W., Juliana, C., Solorzano, L., Kang, S., Wu, J., Datta, P., McCormick, M., Huang, L., McDermott, E., et al. (2010) · Nature Immunology · doi:10.1038/ni.1859 · Cited by 732 · see citing works
Mitochondrial calcium and the permeability transition in cell death
Lemasters, J. J., Theruvath, T. P., Zhong, Z., & Nieminen, A. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.06.009 · Cited by 656 · see citing works
Anti-inflammatory Compounds Parthenolide and Bay 11-7082 Are Direct Inhibitors of the Inflammasome
Juliana, C. A., Fernandes‐Alnemri, T., Wu, J., Datta, P., Solórzano, L., Yu, J., Meng, R., Quong, A. A., Latz, E., Scott, C. P., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.082305 · Cited by 617 · see citing works
Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling
Tal, M. C., Sasai, M., Lee, H. K., Yordy, B., Shadel, G. S., & Iwasaki, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807694106 · Cited by 573 · see citing works
Qu, Y., Franchi, L., Nunez, G., & Dubyak, G. R. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.3.1913 · Cited by 563 · see citing works
Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis
Jones, J. W. M., Kayagaki, N., Brož, P., Henry, T., Newton, K., O’Rourke, K. M., Chan, S. B., Dong, J. J., Qu, Y., Roose-Girma, M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003738107 · Cited by 487 · see citing works
Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease
Chen, Z.-H., Kim, H. P., Sciurba, F. C., Lee, S.-J., Feghali-Bostwick, C., Stolz, D. B., Dhir, R., Landreneau, R. J., Schuchert, M. J., Yousem, S. A., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003316 · Cited by 459 · see citing works
Self-citationVirgin, H. W., & Levine, B. (2009) · Nature Immunology · doi:10.1038/ni.1726 · Cited by 453 · see citing works
P2X7 Receptor Differentially Couples to Distinct Release Pathways for IL-1β in Mouse Macrophage
Pelegrı́n, P., Barroso-Gutierrez, C., & Surprenant, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7147 · Cited by 413 · see citing works
Mortensen, M., Ferguson, D. J. P., Edelmann, M. J., Kessler, B. M., Morten, K., Komatsu, M., & Simon, A. K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913170107 · Cited by 388 · see citing works
Hornung, V., & Latz, E. (2010) · Nature reviews. Immunology · doi:10.1038/nri2690 · Cited by 366 · see citing works
Inflammasomes: too big to miss
Stutz, A., Golenbock, D. T., & Latz, E. (2009) · Journal of Clinical Investigation · doi:10.1172/jci40599 · Cited by 345 · see citing works
Chung, S. W., Liu, X., Macias, A. A., Baron, R. M., & Perrella, M. A. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32730 · Cited by 325 · see citing works
Superoxide dismutase 1 regulates caspase-1 and endotoxic shock
Meissner, F., Molawi, K., & Zychlinsky, A. (2008) · Nature Immunology · doi:10.1038/ni.1633 · Cited by 302 · see citing works
Adinolfi, E., Callegari, M. G., Ferrari, D., Bolognesi, C., Minelli, M., Wieckowski, M. R., Pinton, P., Rizzuto, R., & Virgilio, F. D. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-11-1025 · Cited by 272 · see citing works
Wang, X. M., Kim, H. P., Nakahira, K., Ryter, S. W., & Choi, A. M. K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0712437 · Cited by 227 · see citing works
Self-citationCells depleted of mitochondrial DNA (p0) yield insight into physiological mechanisms
Chandel, N. S., & Schumacker, P. T. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00783-8 · Cited by 198 · see citing works
Eaton, J. S., Lin, Z. P., Sartorelli, A. C., Bonawitz, N. D., & Shadel, G. S. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31604 · Cited by 196 · see citing works
Fredriksson, K., Tjäder, I., Keller, P., Petrovič, N., Ahlman, B. H. J., Scheele, C. C., Wernerman, J., Timmons, J. A., & Rooyackers, O. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003686 · Cited by 168 · see citing works
Establishment of Human Cell Lines Lacking Mitochondrial DNA
Hashiguchi, K., & Zhang-Akiyama, Q.-M. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-521-3_23 · Cited by 141 · see citing works
Antioxidant properties of MitoTEMPOL and its hydroxylamine
Trnka, J., Blaikie, F. H., Logan, A., Smith, R. A. J., & Murphy, M. P. (2008) · Free Radical Research · doi:10.1080/10715760802582183 · Cited by 141 · see citing works
Watanabe, E., Muenzer, J. T., Hawkins, W. G., Davis, C. G., Dixon, D. J., McDunn, J. E., Brackett, D. J., Lerner, M. R., Swanson, P. E., & Hotchkiss, R. S. (2009) · Laboratory Investigation · doi:10.1038/labinvest.2009.8 · Cited by 138 · see citing works
Sepsis induces brain mitochondrial dysfunction.
d’Avila, J. D. C. P., Santiago, A. P. S. A., Amâncio, R. T., Galina, A., Oliveira, M. F., & Bozza, F. A. (2008) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181760c4b · Cited by 134 · see citing works
Aoki, H., Kondo, Y., Aldape, K., Yamamoto, A., Iwado, E., Yokoyama, T., Hollingsworth, E., Kobayashi, R., Hess, K. R., Shinojima, N., et al. (2008) · Autophagy · doi:10.4161/auto.5668 · Cited by 126 · see citing works
Inflammasome mRNA Expression in Human Monocytes during Early Septic Shock
Fahy, R. J., Exline, M. C., Gavrilin, M. A., Bhatt, N. Y., Besecker, B. Y., Sarkar, A., Hollyfield, J. L., Duncan, M., Nagaraja, H. N., Knatz, N. L., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200703-418oc · Cited by 86 · see citing works
Cann, G. M., Guignabert, C., Ying, L., Deshpande, N., Bekker, J. M., Wang, L., Zhou, B., & Rabinovitch, M. (2008) · Developmental Dynamics · doi:10.1002/dvdy.21392 · Cited by 84 · see citing works
Self-citationJiang, J., Stoyanovsky, D. A., Belikova, N. A., Tyurina, Y. Y., Zhao, Q., Tungekar, M. A., Kapralova, V. I., Huang, Z., Mintz, A. H., Greenberger, J. S., et al. (2009) · Radiation Research · doi:10.1667/rr1729.1 · Cited by 76 · see citing works
Garcia‐Marcos, M., Fontanils, U., Aguirre, A., et al. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.08.074 · Cited by 16 · 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
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931 · see citing works
Reactive Oxygen Species in Inflammation and Tissue Injury
Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5149 · Cited by 4,897 · see citing works
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884 · see citing works
The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation
Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133328 · Cited by 3,539 · see citing works
Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310 · see citing works
Mechanism and Regulation of NLRP3 Inflammasome Activation
He, Y., Hara, H., & Núñez, G. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.09.002 · Cited by 2,759 · see citing works
Physiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632 · see citing works
Autophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583 · see citing works
Self-citationMacrophages in atherosclerosis: a dynamic balance
Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3520 · Cited by 2,559 · see citing works
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322 · 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
Self-citationInflammasomes in health and disease
Strowig, T., Henao-Mejia, J., Elinav, E., & Flavell, R. (2012) · Nature · doi:10.1038/nature10759 · Cited by 2,230 · see citing works
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107 · see citing works
Autophagy in infection, inflammation and immunity
Deretic, V., Saitoh, T., & Akira, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3532 · Cited by 1,919 · see citing works
The mitochondrial basis of aging
Sun, N., Youle, R. J., & Finkel, T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.028 · Cited by 1,441 · see citing works
Cholesterol, inflammation and innate immunity.
Tall, A. R., & Yvan-Charvet, L. (2015) · Nature Reviews Immunology · doi:10.1038/nri3793 · Cited by 1,479 · see citing works
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438 · see citing works
Molecular mechanisms regulating NLRP3 inflammasome activation
Jo, E.-K., Kim, J. K., Shin, D.-M., & Sasakawa, C. (2016) · Cellular & Molecular Immunology · doi:10.1038/cmi.2015.95 · Cited by 1,378 · see citing works
Mitochondria in innate immune responses
West, A. P., Shadel, G. S., & Ghosh, S. (2011) · Nature Reviews Immunology · doi:10.1038/nri2975 · Cited by 1,376 · see citing works
RETRACTED 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
RetractedMitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging
Green, D. R., Galluzzi, L., & Kroemer, G. (2011) · Science · doi:10.1126/science.1201940 · Cited by 1,245 · see citing works
Cargo recognition and trafficking in selective autophagy
Stolz, A., Ernst, A., & Dikic, I. (2014) · Nature Cell Biology · doi:10.1038/ncb2979 · Cited by 1,207 · 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
NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria
Zhong, Z., Umemura, A., Sanchez-Lopez, E., Liang, S., Shalapour, S., Wong, J., He, F., Boassa, D., Perkins, G., Ali, S. R., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.057 · Cited by 1,197 · see citing works
Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure
Oka, T., Hikoso, S., Yamaguchi, O., Taneike, M., Takeda, T., Tamai, T., Oyabu, J., Murakawa, T., Nakayama, H., Nishida, K., et al. (2012) · Nature · doi:10.1038/nature10992 · Cited by 1,201 · see citing works
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182 · see citing works
Mitochondrial 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
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
Age-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061 · see citing works
Mitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061 · see citing works
Mitophagy: mechanisms, pathophysiological roles, and analysis
Ding, W.-X., & Yin, X.-M. (2012) · bchm · doi:10.1515/hsz-2012-0119 · Cited by 1,032 · 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
Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β
Dupont, N., Jiang, S., Pilli, M., Ornatowski, W., Bhattacharya, D., & Deretic, V. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.398 · Cited by 967 · see citing works
Mitochondria in the Regulation of Innate and Adaptive Immunity
Weinberg, S. E., Sena, L. A., & Chandel, N. S. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.002 · Cited by 960 · 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
Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842 · 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
VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease
Kim, J., Gupta, R., Blanco, L. P., Yang, S., Shteinfer-Kuzmine, A., Wang, K., Zhu, J., Yoon, H. E., Wang, X., Kerkhofs, M., et al. (2019) · Science · doi:10.1126/science.aav4011 · Cited by 793 · see citing works
Watson, R. O., Manzanillo, P. S., & Cox, J. S. (2012) · Cell · doi:10.1016/j.cell.2012.06.040 · Cited by 755 · see citing works
Mitochondrial reactive oxygen species drive proinflammatory cytokine production
Naik, E., & Dixit, V. M. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110367 · Cited by 783 · see citing works
The inflammasome: an integrated view
Gross, O., Thomas, C. J., Guarda, G., & Tschopp, J. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01046.x · Cited by 778 · see citing works
Mechanism of NLRP3 inflammasome activation
Sutterwala, F. S., Haasken, S., & Cassel, S. L. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12458 · Cited by 736 · see citing works
Mitochondria: master regulators of danger signalling
Galluzzi, L., Kepp, O., & Kroemer, G. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3479 · Cited by 733 · see citing works
TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria
Rathinam, V. A. K., Vanaja, S. K., Waggoner, L., Sokolovska, A., Becker, C., Stuart, L. M., Leong, J. M., & Fitzgerald, K. A. (2012) · Cell · doi:10.1016/j.cell.2012.07.007 · Cited by 729 · see citing works
Self-citationLee, C., Zeng, J., Drew, B. G., Sallam, T., Martin-Montalvo, A., Wan, J., Kim, S.-J., Mehta, H., Hevener, A. L., de Cabo, R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.02.009 · Cited by 715 · see citing works
TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
Pilli, M., Arko-Mensah, J., Ponpuak, M., Roberts, E., Master, S., Mandell, M. A., Dupont, N., Ornatowski, W., Jiang, S., Bradfute, S. B., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.04.015 · Cited by 655 · see citing works
Sterile inflammation in the liver
Kubes, P., & Mehal, W. Z. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.09.008 · Cited by 666 · see citing works
Reactive oxygen species (ROS) in macrophage activation and function in diabetes
Rendra, E., Riabov, V., Mossel, D. M., Sevastyanova, T., Harmsen, M. C., & Kzhyshkowska, J. (2019) · Immunobiology · doi:10.1016/j.imbio.2018.11.010 · Cited by 636 · 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
Walsh, J. G., Muruve, D. A., & Power, C. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3638 · Cited by 637 · see citing works
Bauernfeind, F., Bartok, E., Rieger, A., Franchi, L., Núñez, G., & Hornung, V. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100613 · Cited by 617 · see citing works
Autophagy Links Inflammasomes to Atherosclerotic Progression
Razani, B., Feng, C., Coleman, T., Emanuel, R., Wen, H., Hwang, S., Ting, J. P., Virgin, H. W., Kastan, M. B., & Semenkovich, C. F. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.02.011 · Cited by 601 · 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
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
Blevins, H. M., Xu, Y., Biby, S., & Zhang, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.879021 · Cited by 587 · 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
Mitochondria as signaling organelles
Chandel, N. S. (2014) · BMC Biology · doi:10.1186/1741-7007-12-34 · Cited by 576 · see citing works
Microglial cell dysregulation in brain aging and neurodegeneration
von Bernhardi, R., Eugenín-von Bernhardi, L., & Eugenín, J. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00124 · Cited by 556 · see citing works
Park, J., Min, J.-S., Kim, B., Chae, U.-B., Yun, J. W., Choi, M.-S., Kong, I.-K., Chang, K.-T., & Lee, D.-S. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2014.10.016 · Cited by 529 · see citing works
Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy
Poillet-Perez, L., Despouy, G., Delage-Mourroux, R., & Boyer-Guittaut, M. (2015) · Redox Biology · doi:10.1016/j.redox.2014.12.003 · Cited by 503 · see citing works
Salmonellae interactions with host processes
LaRock, D. L., Chaudhary, A., & Miller, S. I. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3420 · Cited by 502 · see citing works
Caielli, S., Athale, S., Domic, B., Murat, E., Chandra, M., Banchereau, R., Baisch, J., Phelps, K., Clayton, S., Gong, M., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151876 · Cited by 501 · see citing works
Mechanisms of inflammasome activation: recent advances and novel insights
Vanaja, S. K., Rathinam, V. A. K., & Fitzgerald, K. A. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.12.009 · Cited by 499 · see citing works
Self-citationInhibitor 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
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
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
Homeostasis-altering molecular processes as mechanisms of inflammasome activation
Liston, A., & Masters, S. L. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.151 · Cited by 459 · see citing works
Autophagy and cellular immune responses
Ma, Y., Galluzzi, L., Zitvogel, L., & Kroemer, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.017 · Cited by 447 · see citing works
Chronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471 · see citing works
Nakahira, K., Kyung, S.-Y., Rogers, A. J., Gazourian, L., Youn, S., Massaro, A. F., Quintana, C., Osorio, J. C., Wang, Z., Zhao, Y., et al. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001577 · Cited by 445 · see citing works
Self-citationHuang, L. S., Hong, Z., Wu, W., Xiong, S., Zhong, M., Gao, X., Rehman, J., & Malik, A. B. (2020) · Immunity · doi:10.1016/j.immuni.2020.02.002 · Cited by 435 · see citing works
NLRP3 inflammasomes link inflammation and metabolic disease
De Nardo, D., & Latz, E. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.05.004 · Cited by 425 · see citing works
Mitochondria in Cell Senescence: Is Mitophagy the Weakest Link?
Korolchuk, V. I., Miwa, S., Carroll, B., & von Zglinicki, T. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.03.020 · Cited by 409 · see citing works
“Enhanced autophagic clearance of mitochondria suppressed NLRP3 activation (Nakahira et al., 2011; Zhou et al., 2011).”
BackgroundMitochondria in innate immune signaling
Banoth, B., & Cassel, S. L. (2018) · Translational Research · doi:10.1016/j.trsl.2018.07.014 · Cited by 410 · see citing works
Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome
Cho, M.-H., Cho, K., Kang, H.-J., Jeon, E.-Y., Kim, H.-S., Kwon, H.-J., Kim, H.-M., Kim, D.-H., & Yoon, S.-Y. (2014) · Autophagy · doi:10.4161/auto.29647 · Cited by 395 · see citing works
Self-citationMitochondria: diversity in the regulation of the NLRP3 inflammasome
Gurung, P., Lukens, J. R., & Kanneganti, T.-D. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.11.008 · Cited by 393 · see citing works
Signal Transduction by Mitochondrial Oxidants
Finkel, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.271999 · Cited by 390 · see citing works
Lupfer, C., Thomas, P. G., Anand, P. K., Vogel, P., Milasta, S., Martinez, J., Huang, G., Green, M., Kundu, M., Chi, H., et al. (2013) · Nature Immunology · doi:10.1038/ni.2563 · Cited by 384 · see citing works
Todkar, K., Chikhi, L., Desjardins, V., El-Mortada, F., Pépin, G., & Germain, M. (2021) · Nature Communications · doi:10.1038/s41467-021-21984-w · Cited by 382 · see citing works
Immunological impact of cell death signaling driven by radiation on the tumor microenvironment
Rodriguez-Ruiz, M. E., Vitale, I., Harrington, K. J., Melero, I., & Galluzzi, L. (2020) · Nature Immunology · doi:10.1038/s41590-019-0561-4 · Cited by 385 · see citing works
A Crohn’s disease variant in Atg16l1 enhances its degradation by caspase 3
Murthy, A., Li, Y., Peng, I., Reichelt, M., Katakam, A. K., Noubade, R., Roose-Girma, M., DeVoss, J., Diehl, L., Graham, R. R., et al. (2014) · Nature · doi:10.1038/nature13044 · Cited by 381 · see citing works
Redox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377 · 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
Hemolysis-induced lethality involves inflammasome activation by heme
Dutra, F. F., Alves, L. S., Rodrigues, D., Fernandez, P. L., de Oliveira, R. B., Golenbock, D. T., Zamboni, D. S., & Bozza, M. T. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405023111 · Cited by 353 · 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
Manganese Superoxide Dismutase: Guardian of the Powerhouse
Holley, A. K., Bakthavatchalu, V., Velez-Roman, J. M., & St. Clair, D. K. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12107114 · Cited by 358 · see citing works
Modulation of inflammation by autophagy: Consequences for human disease
Netea-Maier, R. T., Plantinga, T. S., van de Veerdonk, F. L., Smit, J. W., & Netea, M. G. (2016) · Autophagy · doi:10.1080/15548627.2015.1071759 · Cited by 349 · see citing works
Inflammation and metabolic cardiomyopathy
Nishida, K., & Otsu, K. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx012 · Cited by 329 · see citing works
Mitochondrial dysfunction and cell senescence: deciphering a complex relationship
Chapman, J., Fielder, E., & Passos, J. F. (2019) · FEBS Letters · doi:10.1002/1873-3468.13498 · Cited by 325 · see citing works
Cloonan, S. M., & Choi, A. M. K. (2016) · Journal of Clinical Investigation · doi:10.1172/jci81113 · Cited by 322 · see citing works
Self-citationInflammasome-independent regulation of IL-1-family cytokines
Netea, M. G., van de Veerdonk, F. L., van der Meer, J. W. M., Dinarello, C. A., & Joosten, L. A. B. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112306 · Cited by 326 · see citing works
Kaarniranta, K., Sinha, D., Blasiak, J., Kauppinen, A., Veréb, Z., Salminen, A., Boulton, M. E., & Petrovski, G. (2013) · Autophagy · doi:10.4161/auto.24546 · Cited by 326 · see citing works
Mitochondria, Oxidative Stress and Innate Immunity
Chen, Y., Zhou, Z., & Min, W. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01487 · Cited by 315 · see citing works
“A recent study elegantly demonstrated that cholesterol overload causes impaired mitochondrial metabolism and mtDNA release, which further triggers AIM2 inflammasome in activated BMDMs (Dang et al., 2017).”
BackgroundInfluentialFreigang, S., Ampenberger, F., Spohn, G., Heer, S., Shamshiev, A. T., Kisielow, J., Hersberger, M., Yamamoto, M., Bachmann, M. F., & Kopf, M. (2011) · European Journal of Immunology · doi:10.1002/eji.201041316 · Cited by 300 · see citing works
Cytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288 · see citing works
Sun, L., Ma, W., Gao, W., Xing, Y., Chen, L., Xia, Z., Zhang, Z., & Dai, Z. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1761-4 · Cited by 296 · see citing works
Moon, J.-S., Nakahira, K., Chung, K.-P., DeNicola, G. M., Koo, M. J., Pabón, M. A., Rooney, K. T., Yoon, J.-H., Ryter, S. W., Stout-Delgado, H., et al. (2016) · Nature Medicine · doi:10.1038/nm.4153 · Cited by 291 · see citing works
Self-citationRetracted
- Authors
- 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., Fitzgerald, K. A., Ryter, S. W., & Choi, A. M. K.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Massachusetts Chan Medical School (US)
- Stanford Medicine (US)
- Corresponding author
- Choi, Augustine M K
- ORCID
- Venue
- Nature Immunology
- Published
- 2010-12-12
- Volume
- 12
- Issue
- 3
- Pages
- 222-230
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3079381
- OpenAlex
- W2113010696
- Cited by
- 3,049
- References
- 49
- Citations by year
- 2026: 178 · 2025: 195 · 2024: 219 · 2023: 189 · 2022: 224 · 2021: 258 · 2020: 248 · 2019: 213 · 2018: 216 · 2017: 183 · 2016: 189 · 2015: 163 · 2014: 166 · 2013: 212 · 2012: 124
- FWCI
- 52.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institutes of Health (1f35hl008554-01)
- National Heart, Lung, and Blood Institute (R01HL055330, R01HL085547, HL08554, R01HL079904, R01HL060234, HL060234-10, HL097005, R03HL097005)
- National Institute of Allergy and Infectious Diseases (R01AI067497, AI057159, R37AI067497, AI083713, U54AI057159, AI-067497, R01AI083713, R56AI067497)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- autophagy, NLRP3 inflammasome, mitochondrial DNA release, LC3B, Beclin-1, caspase-1, IL-1β, IL-18, mitochondrial dysfunction, reactive oxygen species, lipopolysaccharide, ATP, macrophages, sepsis, innate immunity, inflammation
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Autophagy, Carrier Proteins, DNA, Mitochondrial, Flow Cytometry, Immunity, Innate, Caspase 1, Mice, 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
