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Circulating mitochondrial DAMPs cause inflammatory responses to injury
Open accessAbstract
Injury causes a systemic inflammatory response syndrome (SIRS) that is clinically much like sepsis. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors. Similarly, cellular injury can release endogenous 'damage'-associated molecular patterns (DAMPs) that activate innate immunity. Mitochondria are evolutionary endosymbionts that were derived from bacteria and so might bear bacterial molecular motifs. Here we show that injury releases mitochondrial DAMPs (MTDs) into the circulation with functionally important immune consequences. MTDs include formyl peptides and mitochondrial DNA. These activate human polymorphonuclear neutrophils (PMNs) through formyl peptide receptor-1 and Toll-like receptor (TLR) 9, respectively. MTDs promote PMN Ca(2+) flux and phosphorylation of mitogen-activated protein (MAP) kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTDs can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These signal through innate immune pathways identical to those activated in sepsis to create a sepsis-like state. The release of such mitochondrial 'enemies within' by cellular injury is a key link between trauma, inflammation and SIRS.
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“these organelles express biomolecules that resemble those expressed by prokaryotes, such as cardiolipin, double-stranded-hypomethylated DNA and N-formylated peptides12,13”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [13]
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“In human neutrophils, the binding of FPR1 and FPR2 to N-formylated peptides triggers the release of Ca2+ into the cytosol and ultimately leads to the migration and activation of neutrophils13”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [13]
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“Mitochondria are considered as deriving from the endosymbiosis of an α-synfular; proteobacterium (3, 4), providing the organelles many bacterial features (3, 5–9).”
From Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA (2019) · cites this paper as [9]
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“Cardiolipin, N-formylated peptides, mtDNA, ATP and reactive oxygen species are known mitochondrial damage-associated molecular patterns (9, 28–30).”
From Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA (2019) · cites this paper as [9]
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“Mitochondrial debris were observed in blood in the Twin Study (Garrett-Bakelman et al., 2019) and mitochondrial damage-associated molecular patterns (DAMPs) activate innate immune pathways (Banoth and Cassel, 2018; Zhang et al., 2010).”
From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Zhang et al., 2010
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“In an extreme example such as massive trauma, mito-DAMPs, identified as mtDNA and formyl peptides, are acutely released from damaged tissues and cause a sepsis-like systemic inflammatory response syndrome by activating polymorphonuclear cells via TLR9 and formyl peptide receptor-129.”
From Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis (2020) · cites this paper as [29]
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“Like bacteria, mitochondria are formed of an outer and an inner membrane (inner contains cardiolipin)4,5, express formylated peptides6,7, and contain a circular genome with hypomethylated DNA CpG motifs, referred to as mitochondrial DNA (mtDNA)8,9.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [6]
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“Mitochondria and their components (e.g. N-formylated peptides and mtDNA) are recognized as damage-associated molecular patterns (DAMPs), which activate the innate immune system and elicit an inflammatory response6,21–23.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [6]
In the citing paper
“MtDNA has been reported to activate immunity through two distinct pathways, namely Toll-like receptor 9 (TLR9; Zhang et al, 2010;Oka et al, 2012;Liu et al, 2015), and cGAS activation (White et al, 2014;West et al, 2015).”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as Zhang et al, 2010
In the citing paper
“Mitochondria are a source of damage-associated molecular patterns (DAMPs), and among others, mtDNA has been shown to induce a pro-inflammatory state (Zhang et al, 2010;Oka et al, 2012;Wenceslau et al, 2014).”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as Zhang et al, 2010
In the citing paper
“MtDNA is recognized as foreign when found outside of mitochondria and can trigger inflammation (Maekawa et al., 2019; Shimada et al., 2012; Zhang et al., 2010).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Zhang et al., 2010
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“mtDNA is known to localize to endosomes”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Zhang et al., 2010
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“activate DNA sensor and pro-inflammatory mediator TLR9 (Zhang et al., 2010)”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Zhang et al., 2010
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Citations
Cites
Baker, S. P., O’Neill, B., Haddon, W. F., & Long, W. B. (1974) · PubMed · Cited by 7,946
Mizgerd, J. P., Kubo, H., Kutkoski, G. J., Bhagwan, S. D., Scharffetter-Kochanek, K., Beaudet, A. L., & Doerschuk, C. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.8.1357 · Cited by 7,332
Baker, S. P., O’Neill, B., Haddon, W. F., & Long, W. B. (1974) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/00005373-197403000-00001 · Cited by 7,326
Tolerance, Danger, and the Extended Family
Matzinger, P. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.005015 · Cited by 4,848
Approaching the asymptote? Evolution and revolution in immunology.Preprint
Janeway, C. (1989) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1989.054.01.003 · Cited by 3,396
On the origin of mitosing cells
Sagan, L. (1967) · Journal of Theoretical Biology · doi:10.1016/0022-5193(67)90079-3 · Cited by 1,870
The mitochondrial genome: structure, transcription, translation and replication
Taanman, J.-W. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00161-3 · Cited by 1,635
Seong, S., & Matzinger, P. (2004) · Nature reviews. Immunology · doi:10.1038/nri1372 · Cited by 1,224
Toll-like receptors stimulate human neutrophil function
Hayashi, F., Means, T. K., & Luster, A. D. (2003) · Blood · doi:10.1182/blood-2003-04-1078 · Cited by 939
N-formylmethionyl peptides as chemoattractants for leucocytes.
Schiffmann, E., Corcoran, B. A., & Wahl, S. M. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.3.1059 · Cited by 889
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Iba, T., & Levy, J. H. (2017) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13911 · Cited by 558
Obesity, Hypertension, and Cardiac Dysfunction
Mouton, A. J., Li, X., Hall, M. E., & Hall, J. E. (2020) · Circulation Research · doi:10.1161/circresaha.119.312321 · Cited by 561
Sepsis-induced myocardial dysfunction: pathophysiology and management
Kakihana, Y., Ito, T., Nakahara, M., Yamaguchi, K., & Yasuda, T. (2016) · Journal of Intensive Care · doi:10.1186/s40560-016-0148-1 · Cited by 564
Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke
Alsbrook, D. L., Napoli, M. D., Bhatia, K., Biller, J., Andalib, S., Hinduja, A., Rodrigues, R., Rodriguez, M., Sabbagh, S. Y., Selim, M. H., et al. (2023) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-023-01282-2 · Cited by 573
New Approaches to Sepsis: Molecular Diagnostics and Biomarkers
Reinhart, K., Bauer, M. W., Riedemann, N. C., & Hartog, C. S. (2012) · Clinical Microbiology Reviews · doi:10.1128/cmr.00016-12 · Cited by 546
The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing
Johnson, B. Z., Stevenson, A. W., Prêle, C. M., Fear, M. W., & Wood, F. M. (2020) · Biomedicines · doi:10.3390/biomedicines8050101 · Cited by 557
Neutrophils in the tumor microenvironment
Powell, D. R., & Huttenlocher, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2015.11.008 · Cited by 578
Mitochondrial dysfunction and the inflammatory response
López-Armada, M. J., Riveiro-Naveira, R. R., Vaamonde‐García, C., & Valcarcel‐Ares, M. N. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.01.003 · Cited by 528
Linking cellular stress responses to systemic homeostasis
Galluzzi, L., Yamazaki, T., & Kroemer, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0068-0 · Cited by 556
Mack, M. (2017) · Matrix Biology · doi:10.1016/j.matbio.2017.11.010 · Cited by 535
Slavich, G. M. (2020) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032816-045159 · Cited by 502
Cancer and Inflammation: An Old Intuition with Rapidly Evolving New Concepts
Trinchieri, G. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075008 · Cited by 522
An Integrated Clinico-Metabolomic Model Improves Prediction of Death in Sepsis
Langley, R. J., Tsalik, E. L., van Velkinburgh, J. C., Glickman, S. W., Rice, B., Wang, C., Chen, B., Carin, L., Suarez, A., Mohney, R. P., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005893 · Cited by 516
Extracellular Histones Are Mediators of Death through TLR2 and TLR4 in Mouse Fatal Liver Injury
Xu, J., Zhang, X., Monestier, M., Esmon, N. L., & Esmon, C. T. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003930 · Cited by 504
Nox enzymes and new thinking on reactive oxygen: A double-edged sword revisited
Lambeth, J. D., & Neish, A. S. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104651 · Cited by 495
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
Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9
Garcia-Martinez, I., Santoro, N., Chen, Y., Hoque, R., Ouyang, X., Caprio, S., Shlomchik, M. J., Coffman, R. L., Candia, A., & Mehal, W. Z. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83885 · Cited by 498
Self-citationCalder, P. C., Bosco, N., Bourdet‐Sicard, R., Capuron, L., Delzenne, N. M., Dore, J. M., Franceschi, C., Lehtinen, M. J., Recker, T., Salvioli, S., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.09.001 · Cited by 524
Pattern recognition receptors and central nervous system repair
Kigerl, K. A., de Rivero Vaccari, J. P., Dietrich, W. D., Popovich, P. G., & Keane, R. W. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.01.001 · Cited by 490
Sawka, M. N., Leon, L. R., Montain, S. J., & Sonna, L. A. (2011) · Comprehensive Physiology · doi:10.1002/cphy.c100082 · Cited by 470
The NLRP3 inflammasome: contributions to inflammation-related diseases
Chen, Y., Ye, X., Escames, G., Lei, W., Zhang, X., Li, M., Jing, T., Yao, Y., Qiu, Z., Wang, Z., et al. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00462-9 · Cited by 492
“molecular patterns (DAMPs), which are endogenous molecules derived from dying cells [3].”
BackgroundSelf-citationMitochondrial Function, Biology, and Role in Disease
Murphy, E., Ardehali, H., Balaban, R. S., Lisa, F. D., Dorn, G. W., Kitsis, R. N., Otsu, K., Ping, P., Rizzuto, R., Sack, M. N., et al. (2016) · Circulation Research · doi:10.1161/res.0000000000000104 · Cited by 476
Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain
Shichita, T., Hasegawa, E., Kimura, A., Morita, R., Sakaguchi, R., Takada, I., Sekiya, T., Ooboshi, H., Kitazono, T., Yanagawa, T., et al. (2012) · Nature Medicine · doi:10.1038/nm.2749 · Cited by 455
AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function
Dugan, L. L., You, Y.-H., Ali, S. S., Diamond-Stanic, M. K., Miyamoto, S., Declèves, A., Andreyev, A. Y., Quach, T., Ly, S., Shekhtman, G., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66218 · Cited by 457
Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding
Iskander, K. N., Osuchowski, M. F., Stearns-Kurosawa, D. J., Kurosawa, S., Stepien, D. M., Valentine, C., & Remick, D. G. (2013) · Physiological Reviews · doi:10.1152/physrev.00037.2012 · Cited by 470
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453
The rise of mitochondria in medicine
Picard, M. A., Wallace, D. C., & Burelle, Y. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.07.003 · Cited by 475
Diverse roles of mitochondria in ischemic stroke
Yang, J., Mukda, S., & Chen, S. (2018) · Redox Biology · doi:10.1016/j.redox.2018.03.002 · Cited by 459
Qiang, X., Yang, W.-L., Wu, R., Zhou, M., Jacob, A., Dong, W., Kuncewitch, M., Ji, Y., Yang, H., Wang, H., et al. (2013) · Nature Medicine · doi:10.1038/nm.3368 · Cited by 441
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
Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses
Garg, A. D., & Agostinis, P. (2017) · Immunological Reviews · doi:10.1111/imr.12574 · Cited by 451
Picca, A., Calvani, R., Coelho‐Júnior, H. J., Landi, F., Bernabei, R., & Marzetti, E. (2020) · Antioxidants · doi:10.3390/antiox9080647 · Cited by 465
Mitochondria Know No Boundaries: Mechanisms and Functions of Intercellular Mitochondrial Transfer
Torralba, D., Baixauli, F., & Sánchez-Madrid, F. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00107 · Cited by 440
Volarević, V., Djokovic, B., Gazdic, M., Harrell, C. R., Fellabaum, C., Djonov, V., & Arsenijević, N. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0518-9 · Cited by 445
da Silveira, W. A., Fazelinia, H., Rosenthal, S. B., Laiakis, E. C., Kim, M. S., Meydan, C., Kidane, Y., Rathi, K. S., Smith, S. M., Stear, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.11.002 · Cited by 402
“, 2019) and mitochondrial damageassociated molecular patterns (DAMPs) activate innate immune pathways (Banoth and Cassel, 2018; Zhang et al., 2010).”
More friend than foe: the emerging role of neutrophils in tissue repair
Peiseler, M., & Kubes, P. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124616 · Cited by 423
Intercellular mitochondrial transfer as a means of tissue revitalization
Liu, D., Gao, Y., Liu, J., Huang, Y., Yin, J., Feng, Y., Shi, L., Meloni, B. P., Zhang, C., Zheng, M., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00440-z · Cited by 403
Source of chronic inflammation in aging
Sanada, F., Taniyama, Y., Muratsu, J., Otsu, R., Shimizu, H., Rakugi, H., & Morishita, R. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00012 · Cited by 413
Stark, K., Eckart, A., Haidari, S., Tirniceriu, A., Lorenz, M., von Brühl, M.-L., Gärtner, F., Khandoga, A. G., Legate, K. R., Pless, R., et al. (2013) · Nature Immunology · doi:10.1038/ni.2477 · Cited by 447
Mitochondrial Damage-Associated Molecular Patterns: From Inflammatory Signaling to Human Diseases
Grazioli, S., & Pugin, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00832 · Cited by 429
Many stimuli pull the necrotic trigger, an overview
Vanlangenakker, N., Berghe, T. V., & Vandenabeele, P. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.164 · Cited by 418
Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death
Garg, A. D., Galluzzi, L., Apétoh, L., Baert, T., Birge, R. B., Pedro, J. M. B., Breckpot, K., Brough, D., Chaurio, R. A., Cirone, M., et al. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00588 · Cited by 420
Mitochondria in innate immune signaling
Banoth, B., & Cassel, S. L. (2018) · Translational Research · doi:10.1016/j.trsl.2018.07.014 · Cited by 410
Pinti, M., Cevenini, E., Nasi, M., De Biasi, S., Salvioli, S., Monti, D., Benatti, S., Gibellini, L., Cotichini, R., Stazi, M. A., et al. (2014) · European Journal of Immunology · doi:10.1002/eji.201343921 · Cited by 409
Engelmann, C., Clària, J., Szabó, G., Bosch, J., & Bernardi, M. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.01.002 · Cited by 431
Vezzani, A., Maroso, M., Balosso, S., Sanchez, M.-A., & Bartfai, T. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.03.018 · Cited by 362
Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair
Lafuse, W. P., Wozniak, D. J., & Rajaram, M. V. S. (2020) · Cells · doi:10.3390/cells10010051 · Cited by 413
Mitochondrial dysfunction in inherited renal disease and acute kidney injury
Emma, F., Montini, G., Parikh, S. M., & Salviati, L. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.214 · Cited by 400
NASH is an Infl ammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications
Farrell, G. C., Rooyen, D. M. V., Gan, L. T., & Chitturi, S. (2012) · Gut and Liver · doi:10.5009/gnl.2012.6.2.149 · Cited by 408
Zhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 425
Mitochondria: 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
The Acute Respiratory Distress Syndrome: From Mechanism to Translation
Han, S., & Mallampalli, R. K. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402513 · Cited by 404
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
MD-2 is required for disulfide HMGB1–dependent TLR4 signaling
Yang, H., Wang, H., Ju, Z., Ragab, A. A. Y., Lundbäck, P., Long, W., Valdés‐Ferrer, S. I., He, M., Pribis, J. P., Li, J., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20141318 · Cited by 379
Mitochondrial allostatic load puts the 'gluc' back in glucocorticoids
Picard, M., Juster, R.-P., & McEwen, B. S. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.22 · Cited by 405
Beclin-1-Dependent Autophagy Protects the Heart During Sepsis
Sun, Y., Yao, X., Zhang, Q.-J., Zhu, M., Liu, Z.-P., Ci, B., Xie, Y., Carlson, D., Rothermel, B. A., Sun, Y., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.032821 · Cited by 381
Self-citationMartin, K. E., & Garcı́a, A. J. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.038 · Cited by 384
Liver ischaemia–reperfusion injury: a new understanding of the role of innate immunity
Hirao, H., Nakamura, K., & Kupiec‐Weglinski, J. W. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00549-8 · Cited by 384
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
Dealing with danger in the CNS: the response of the immune system to injury
Gadani, S. P., Walsh, J. T., Lukens, J. R., & Kipnis, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.019 · Cited by 342
The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases
Nakahira, K., Hisata, S., & Choi, A. M. K. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6407 · Cited by 363
Inflammaging decreases adaptive and innate immune responses in mice and humans
Frasca, D., & Blomberg, B. B. (2016) · Biogerontology · doi:10.1007/s10522-015-9578-8 · Cited by 357
Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?
Kuo, C., Babuharisankar, A. P., Lin, Y., Lien, H., Lo, Y. K., Chou, H.-Y., Tangeda, V., Cheng, L.-C., Cheng, A. N., & Lee, A. Y. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00859-2 · Cited by 367
“The intracellular/extracellular transport of the mtDNA is reportedly possible through the extracellular vesicles (EVs) [158] which helps the mtDNA to trigger pro-inflammatory cytokines leading to its own degradation [159].”
BackgroundA mitochondrial bioenergetic etiology of disease
Wallace, D. C. (2013) · Journal of Clinical Investigation · doi:10.1172/jci61398 · Cited by 342
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
DAMPs, MAMPs, and NAMPs in plant innate immunity
Choi, H. W., & Klessig, D. F. (2016) · BMC Plant Biology · doi:10.1186/s12870-016-0921-2 · Cited by 378
Mitochondrial genetic medicine
Wallace, D. C. (2018) · Nature Genetics · doi:10.1038/s41588-018-0264-z · Cited by 344
The role of platelets in immune-mediated inflammatory diseases
Scherlinger, M., Richez, C., Tsokos, G. C., Boilard, É., & Blanco, P. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00834-4 · Cited by 375
Tissue-based class control: the other side of tolerance
Matzinger, P., & Kamala, T. (2011) · Nature reviews. Immunology · doi:10.1038/nri2940 · Cited by 353
Safavynia, S. A., & Goldstein, P. A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00752 · Cited by 356
New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation
Yang, H., Biermann, M. H. C., Brauner, J., Liu, Y., Zhao, Y., & i, M. H. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00302 · Cited by 346
Terminally Differentiated CD8 + T Cells Negatively Affect Bone Regeneration in Humans
Reinke, S., Geißler, S., Taylor, W. R., Schmidt‐Bleek, K., Juelke, K., Schwachmeyer, V., Dahne, M., Hartwig, T., Akyüz, L., Meisel, C., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004754 · Cited by 336
Regenerative abilities of mesenchymal stem cells through mitochondrial transfer
Paliwal, S., Chaudhuri, R., Agrawal, A., & Mohanty, S. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0429-1 · Cited by 343
Anders, H., & Schaefer, L. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014010117 · Cited by 341
Ischemia and Reperfusion Injury in Kidney Transplantation: Relevant Mechanisms in Injury and Repair
Nieuwenhuijs‐Moeke, G. J., Pischke, S. E., Berger, S. P., Sanders, J., Pol, R. A., Struys, M. M. R. F., Ploeg, R. J., & Leuvenink, H. G. D. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9010253 · Cited by 336
Mitochondrial DNA Release in Innate Immune Signaling
Newman, L. E., & Shadel, G. S. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104401 · Cited by 349
“Furthermore, mtDNA can gain access to the circulatory system and be detected as so-called circulating cell-free mtDNA (CCF-mtDNA) (48–52).”
BackgroundWang, H., Li, T., Chen, S., Gu, Y., & Ye, S. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39296 · Cited by 325
Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum
Vieira‐de‐Abreu, A., Campbell, R. A., Weyrich, A. S., & Zimmerman, G. A. (2011) · Seminars in Immunopathology · doi:10.1007/s00281-011-0286-4 · Cited by 328
An, P., Wei, L.-L., Zhao, S., Sverdlov, D. Y., Vaid, K. A., Miyamoto, M., Kuramitsu, K., Lai, M., & Popov, Y. V. (2020) · Nature Communications · doi:10.1038/s41467-020-16092-0 · Cited by 319
Mitochondria in Ischemic Stroke: New Insight and Implications
Liu, F., Lu, J., Manaenko, A., Tang, J., & Hu, Q. (2018) · Aging and Disease · doi:10.14336/ad.2017.1126 · Cited by 332
Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX
Ney, P. A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.02.022 · Cited by 328
Idiosyncratic Adverse Drug Reactions: Current Concepts
Uetrecht, J., & Naisbitt, D. J. (2013) · Pharmacological Reviews · doi:10.1124/pr.113.007450 · Cited by 320
Psychological Stress and Mitochondria: A Conceptual Framework
Picard, M. A., & McEwen, B. S. (2018) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000544 · Cited by 328
Wei, X., Shao, B., He, Z., Ye, T., Luo, M., Sang, Y., Liang, X., Wang, W., Luo, S., Yang, S., et al. (2015) · Cell Research · doi:10.1038/cr.2015.9 · Cited by 309
Prognostic utility and characterization of cell-free DNA in patients with severe sepsis
Dwivedi, D. J., Toltl, L. J., Swystun, L. L., Pogue, J., Liaw, K., Weitz, J. I., Cook, D. J., Fox‐Robichaud, A., Liaw, P. C., & the Canadian Critical Care Translational Biology Group (2012) · Critical Care · doi:10.1186/cc11466 · Cited by 316
Puhm, F., Afonyushkin, T., Resch, U., Obermayer, G., Rohde, M., Penz, T., Schuster, M., Wagner, G., Rendeiro, A. F., Melki, I., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.314601 · Cited by 306
The immune response to surgery and trauma
Marik, P. E., & Flemmer, M. C. (2012) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e318265cf87 · Cited by 314
Endometriosis, a disease of the macrophage
Capobianco, A. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00009 · Cited by 309
Picard, M., McManus, M. J., Gray, J. D., Nasca, C., Moffat, C., Kopinski, P. K., Seifert, E. L., McEwen, B. S., & Wallace, D. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515733112 · Cited by 293
Marques, P. E., Amaral, S. S., Pires, D. A., Nogueira, L. L., Soriani, F. M., Lima, B. H. F., Lopes, G. A. O., Russo, R. C., Ávila, T. V., Melgaço, J. G., et al. (2012) · Hepatology · doi:10.1002/hep.25801 · Cited by 332
Toll‐like receptors in alcoholic liver disease, non‐alcoholic steatohepatitis and carcinogenesis
Roh, Y. S., & Seki, E. (2013) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12019 · Cited by 309
Salminen, A., Ojala, J. O., Kaarniranta, K., & Kauppinen, A. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0962-0 · Cited by 308
A mitochondrial etiology of Alzheimer and Parkinson disease
Coskun, P. E., Wyrembak, J., Schriner, S. E., Chen, H.-W., Marciniack, C., LaFerla, F. M., & Wallace, D. C. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.008 · Cited by 297
The role of neutrophils in immune dysfunction during severe inflammation
Leliefeld, P. H. C., Wessels, C. M., Leenen, L. P. H., Koenderman, L., & Pillay, J. (2016) · Critical Care · doi:10.1186/s13054-016-1250-4 · Cited by 312
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
Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles
Bonora, M., Wieckowski, M. R., Sinclair, D. A., Kroemer, G., Pinton, P., & Galluzzi, L. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0074-0 · Cited by 308
Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases
Duvvuri, B., & Lood, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00502 · Cited by 282
Chronic Critical Illness and the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome
Hawkins, R. B., Raymond, S. L., Stortz, J. A., Horiguchi, H., Brakenridge, S. C., Gardner, A. K., Efron, P. A., Bihorac, A., Segal, M. S., Moore, F. A., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01511 · Cited by 304
Mahrouf‐Yorgov, M., Augeul, L., Silva, C. C. D., Jourdan, M., Rigolet, M., Manin, S., Ferrera, R., Ovize, M., Henry, A., Guguin, A., et al. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.51 · Cited by 300
Badylak, S. F. (2014) · Annals of Biomedical Engineering · doi:10.1007/s10439-013-0963-7 · Cited by 307
Metadata
- Authors
- Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Queen Mary University of London (GB)
- Corresponding author
- Hauser, Carl J.
- ORCID
- Venue
- Nature
- Published
- 2010-03
- Volume
- 464
- Issue
- 7285
- Pages
- 104-107
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2843437
- OpenAlex
- W2134219545
- Cited by
- 3,812
- References
- 34
- Citations by year
- 2026: 253 · 2025: 254 · 2024: 268 · 2023: 266 · 2022: 267 · 2021: 294 · 2020: 275 · 2019: 243 · 2018: 246 · 2017: 252 · 2016: 248 · 2015: 230 · 2014: 196 · 2013: 176 · 2012: 148
- FWCI
- 70.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Defense
- National Institute of General Medical Sciences (R01GM051477, R01GM059179)
- Congressionally Directed Medical Research Programs
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Keywords
- mitochondrial DAMPs, mitochondrial damage-associated molecular patterns, mitochondrial DNA, formyl peptides, FPR1, TLR9, neutrophils, systemic inflammatory response syndrome, trauma (physical injury), innate immunity, neutrophil degranulation, MAPK signaling, target organ damage
- MeSH terms
- Animals, Cells, Cultured, DNA, Mitochondrial, Femur, Humans, Immunity, Innate, Liver, Male, Mitochondria, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, Phosphorylation, Wounds and Injuries, Rats, Sprague-Dawley, Muscle, Skeletal, Systemic Inflammatory Response Syndrome, Sepsis, CpG Islands, Calcium Signaling, Mitogen-Activated Protein Kinases, Receptors, Formyl Peptide, Fractures, Bone, Toll-Like Receptor 9, Rats, Acute Lung Injury
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