Cited by 136Immune cells in cancerMitochondrial Function and PathologyCancer, Hypoxia, and Metabolism

The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.

Abolition of mitochondrial substrate‐level phosphorylation by itaconic acid produced by LPS‐induced Irg1 expression in cells of murine macrophage lineage

Németh, Beata, Doczi, Judit, Csete, Daniel, Kacso, Gergely, Ravasz, Dora, Adams, Daniel, Kiss, Gergely, Nagy, Adam M., Horvath, Gergo, Tretter, Laszlo, Mócsai, Attila, Csépáinyi‐Kömi, Roland, Iordanov, Iordan, Adam‐Vizi, Vera, Chinopoulos, Christos·2016·The FASEB Journal

DOI 10.1096/fj.15-279398

Open this paper in CoChat — free account

Abstract

Itaconate is a nonamino organic acid exhibiting antimicrobial effects. It has been recently identified in cells of macrophage lineage as a product of an enzyme encoded by immunoresponsive gene 1 ( Irg1 ), acting on the citric acid cycle intermediate cis‐aconitate. In mitochondria, itaconate can be converted by succinate‐coenzyme A (CoA) ligase to itaconyl‐CoA at the expense of ATP (or GTP), and is also a weak competitive inhibitor of complex II. Here, we investigated specific bioenergetic effects of increased itaconate production mediated by LPS‐induced stimulation of Irg1 in murine bone marrow‐derived macrophages (BMDM) and RAW‐264.7 cells. In rotenone‐treated macrophage cells, stimulation by LPS led to impairment in substrate‐level phosphorylation (SLP) of in situ mitochondria, deduced by a reversal in the directionality of the adenine nucleotide translocase operation. In RAW‐264.7 cells, the LPS‐induced impairment in SLP was reversed by short‐interfering RNA(siRNA)—but not scrambled siRNA—treatment directed against Irg1. LPS dose‐dependently inhibited oxygen consumption rates (61‐91%) and elevated glycolysis rates (>21%) in BMDM but not RAW‐264.7 cells, studied under various metabolic conditions. In isolated mouse liver mitochondria treated with rotenone, itaconate dose‐dependently (0.5‐2 mM) reversed the operation of adenine nucleotide translocase, implying impairment in SLP, an effect that was partially mimicked by malonate. However, malonate yielded greater ADP‐induced depolarizations (3‐19%) than itaconate. We postulate that itaconate abolishes SLP due to 1) a “CoA trap” in the form of itaconyl‐CoA that negatively affects the upstream supply of succinyl‐CoA from the α‐ketoglutarate dehydrogenase complex; 2) depletion of ATP (or GTP), which are required for the thioesterification by succinate‐CoA ligase; and 3) inhibition of complex II leading to a buildup of succinate which shifts succinate‐CoA ligase equilibrium toward ATP (or GTP) utilization. Our results support the notion that Irg1 ‐expressing cells of macrophage lineage lose the capacity of mitochondrial SLP for producing itaconate during mounting of an immune defense.—Németh, B., Doczi, J., Csete, D., Kacso, G., Ravasz, D., Adams, D., Kiss, G., Nagy, A. M., Horvath, G., Tretter, L., Mócsai, A., Csépányi‐Kömi, R., Iordanov, I., Adam‐Vizi, V., Chinopoulos, C. Abolition of mitochondrial substrate‐level phosphorylation by itaconic acid produced by LPS‐induced Irg1 expression in cells of murine macrophage lineage. FASEB J. 30, 286‐300 (2016). www.fasebj.org

Integrity signals

Registry

Crossref · 10.1096/fj.15-279398

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

1 retracted

Activated macrophages utilize glycolytic ATP to maintain mitochondrial membrane potential and prevent apoptotic cell death
Garedew, A., Henderson, S. O., & Moncada, S. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.27 · Cited by 124
Retracted
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176
A new collection method for the evaluation of nasal mucus proteins
Ruocco, L. A., Fattori, Romanelli, Martelloni, L., Casani, Samolewska, & Rezzonico (1998) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.1998.00312.x · Cited by 1,296
Toll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation
Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., et al. (2010) · Blood · doi:10.1182/blood-2009-10-249540 · Cited by 1,246
Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
Hoebe, K. H. N., Du, X., Georgel, P., Janssen, E. M., Tabeta, K., Kim, S. O., Goode, J., Lin, P., Mann, N., Mudd, S., et al. (2003) · Nature · doi:10.1038/nature01889 · Cited by 1,232
Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
Michelucci, A., Cordes, T., Ghelfi, J., Pailot, A., Reiling, N., Goldmann, O., Binz, T., Wegner, A., Tallam, A., Rausell, A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218599110 · Cited by 1,191
Substrate Fate in Activated Macrophages: A Comparison between Innate, Classic, and Alternative Activation
Rodríguez-Prados, J.-C., Través, P. G., Cuenca, J., Rico, D., Aragonés, J., Martín-Sanz, P., Cascante, M., & Boscá, L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901698 · Cited by 1,022
Safranine as a probe of the mitochondrial membrane potential
Åkerman, K. E. O., & Wikström, M. K. F. (1976) · FEBS Letters · doi:10.1016/0014-5793(76)80434-6 · Cited by 793
Succinate: a metabolic signal in inflammation
Mills, E., & O’Neill, L. A. J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.11.008 · Cited by 741

Show all 65 references

Sorted by citations

Immunometabolism governs dendritic cell and macrophage function
O'Neill, L. A. J., & Pearce, E. J. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20151570 · Cited by 1,779
Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation
Lampropoulou, V., Sergushichev, A., Bambousková, M., Nair, S., Vincent, E. E., Loginicheva, E., Cervantes‐Barragán, L., Ma, X., Huang, S. C., Griss, T., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.004 · Cited by 1,583
Macrophage Immunometabolism: Where Are We (Going)?
den Bossche, J. V., O'Neill, L. A. J., & Menon, D. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.03.001 · Cited by 1,187
HIF1α and metabolic reprogramming in inflammation
Corcoran, S. E., & O'Neill, L. A. J. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84431 · Cited by 814
Glycolysis – a key player in the inflammatory response
Soto‐Heredero, G., Heras, M. M. G. D. L., Gabandé‐Rodríguez, E., Oller, J., & Mittelbrunn, M. (2020) · FEBS Journal · doi:10.1111/febs.15327 · Cited by 660
Itaconate: the poster child of metabolic reprogramming in macrophage function
O'Neill, L. A. J., & Artyomov, M. N. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0128-5 · Cited by 643
Metabolic Regulation of Macrophage Polarization in Cancer
Mehla, K., & Singh, P. K. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.10.007 · Cited by 621
A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation
Williams, N. C., & O'Neill, L. A. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00141 · Cited by 599
Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis
Tretter, L., Patócs, A., & Chinopoulos, C. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.03.012 · Cited by 550
Self-citation
Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels
Cordes, T., Wallace, M., Michelucci, A., Divakaruni, A. S., Sapcariu, S. C., Sousa, C., Koseki, H., Cabrales, P., Murphy, A. N., Hiller, K., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.685792 · Cited by 526
Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase
Palmieri, E. M., Gonzalez-Cotto, M., Baseler, W. A., Davies, L. C., Ghesquière, B., Maio, N., Rice, C. M., Rouault, T. A., Cassel, T., Higashi, R. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14433-7 · Cited by 483
Krebs cycle Reborn in macrophage immunometabolism
Ryan, D. G., & O'Neill, L. A. J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-081619-104850 · Cited by 444
Coupling Krebs cycle metabolites to signalling in immunity and cancer
Ryan, D. G., Murphy, M. P., Frezza, C., Prag, H. A., Chouchani, E. T., O’Neill, L. A., & Mills, E. L. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0014-7 · Cited by 398
Gut Microbiome Dysbiosis and Immunometabolism: New Frontiers for Treatment of Metabolic Diseases
Belizário, J. E., Faintuch, J., & Garay-Malpartida, M. (2018) · Mediators of Inflammation · doi:10.1155/2018/2037838 · Cited by 341
Metabolic Modulation in Macrophage Effector Function
Diskin, C., & Pålsson‐McDermott, E. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00270 · Cited by 310
BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases
Papathanassiu, A. E., Ko, J., Imprialou, M., Bagnati, M., Srivastava, P. K., Vu, H., Cucchi, D., McAdoo, S. P., Ananieva, E. A., Mauro, C., et al. (2017) · Nature Communications · doi:10.1038/ncomms16040 · Cited by 258
The Immunomodulatory Potential of the Metabolite Itaconate
Hooftman, A., & O'Neill, L. A. J. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.05.007 · Cited by 236
ACOD1 in immunometabolism and disease
Wu, R., Chen, F., Wang, N., Tang, D., & Kang, R. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0489-5 · Cited by 223
Metabolic Remodeling, Inflammasome Activation, and Pyroptosis in Macrophages Stimulated by Porphyromonas gingivalis and Its Outer Membrane Vesicles
Fleetwood, A. J., Lee, M. K. S., Singleton, W., Achuthan, A. A., Lee, M.-C., O’brien-simpson, N. M., Cook, A. D., Murphy, A. J., Dashper, S. G., Reynolds, E. C., et al. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00351 · Cited by 212
Integrating immunometabolism and macrophage diversity
Artyomov, M. N., Sergushichev, A., & Schilling, J. D. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.10.004 · Cited by 195
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism
Chen, F., Elgaher, W. A. M., Winterhoff, M., Büssow, K., Waqas, S. F., Graner, E., Pires‐Afonso, Y., Perez, L. C., de la Vega, L., Sahini, N., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00577-x · Cited by 175
Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis
Namba, T., Dóczi, J., Pinson, A., Xing, L., Kalebic, N., Wilsch‐Bräuninger, M., Long, K. R., Vaid, S., Lauer, J. L., Bogdanova, A. I., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.11.027 · Cited by 161
Self-citation
Itaconate modulates tricarboxylic acid and redox metabolism to mitigate reperfusion injury
Cordes, T., Lucas, A., Divakaruni, A. S., Murphy, A. N., Cabrales, P., & Metallo, C. M. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.11.019 · Cited by 156
Krebs cycle rewired for macrophage and dendritic cell effector functions
Ryan, D. G., & O'Neill, L. A. J. (2017) · FEBS Letters · doi:10.1002/1873-3468.12744 · Cited by 154
Role of Macrophages in Wound HealingPreprint
Willenborg, S., Injarabian, L., & Eming, S. A. (2022) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041216 · Cited by 150
Mitochondrial metabolites: undercover signalling molecules
Frezza, C. (2017) · Interface Focus · doi:10.1098/rsfs.2016.0100 · Cited by 136
Effects of Interferons and Viruses on Metabolism
Fritsch, S. D., & Weichhart, T. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00630 · Cited by 136
Cellular succinate metabolism and signaling in inflammation: implications for therapeutic intervention
Huang, H., Li, G., He, Y., Chen, J., Yan, J., Zhang, Q., Li, L., & Cai, X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1404441 · Cited by 155
Mesaconate is synthesized from itaconate and exerts immunomodulatory effects in macrophages
He, W., Henne, A., Lauterbach, M., Geißmar, E., Nikolka, F., Kho, C., Heinz, A., Dostert, C., Grusdat, M., Cordes, T., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00565-1 · Cited by 119
Biochemistry of proinflammatory macrophage activation
Nonnenmacher, Y., & Hiller, K. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2784-1 · Cited by 112
G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus
Riddy, D. M., Delerive, P., Summers, R. J., Sexton, P. M., & Langmead, C. J. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014373 · Cited by 108
Vitamin D endocrinology on the cross-road between immunity and metabolism
Vanherwegen, A.-S., Gysemans, C. A., & Mathieu, C. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.04.018 · Cited by 107
Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS
Zhu, X., Guo, Y., Liu, Z., Yang, J., Tang, H., & Wang, Y. (2021) · Scientific Reports · doi:10.1038/s41598-021-97352-x · Cited by 107
Itaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice
Weiss, J. M., Palmieri, E. M., Gonzalez-Cotto, M., Bettencourt, I. A., Megill, E., Snyder, N. W., & McVicar, D. W. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00801-2 · Cited by 98
Glutamine via α-ketoglutarate dehydrogenase provides succinyl-CoA for heme synthesis during erythropoiesis
Burch, J. S., Marcero, J. R., Maschek, J. A., Cox, J. E., Jackson, L. K., Medlock, A. E., Phillips, J. D., & Dailey, H. A. (2018) · Blood · doi:10.1182/blood-2018-01-829036 · Cited by 92
Immunometabolism of Macrophages in Bacterial Infections
Galli, G., & Saleh, M. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.607650 · Cited by 96
The Role of Tricarboxylic Acid Cycle Metabolites in Viral Infections
Sánchez‐García, F. J., Pérez-Hernández, C. A., Rodríguez-Murillo, M., & Moreno‐Altamirano, M. M. B. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.725043 · Cited by 89
Press-pulse: a novel therapeutic strategy for the metabolic management of cancer
Seyfried, T. N., Yu, G. W., Maroon, J. C., & D’Agostino, D. P. (2017) · Nutrition & Metabolism · doi:10.1186/s12986-017-0178-2 · Cited by 86
Metabolic Reprogramming in Mitochondria of Myeloid Cells
Zuo, H., & Wan, Y. (2019) · Cells · doi:10.3390/cells9010005 · Cited by 83
Itaconate Alters Succinate and Coenzyme A Metabolism via Inhibition of Mitochondrial Complex II and Methylmalonyl-CoA Mutase
Cordes, T., & Metallo, C. M. (2021) · Metabolites · doi:10.3390/metabo11020117 · Cited by 75
Macrophage Responses to Environmental Stimuli During Homeostasis and Disease
Rasheed, A., & Rayner, K. J. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab004 · Cited by 83
The role of metabolic reprogramming of tumor-associated macrophages in shaping the immunosuppressive tumor microenvironment
Li, L., & Tian, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114504 · Cited by 75
TCA cycle signalling and the evolution of eukaryotes
Ryan, D. G., Frezza, C., & O'Neill, L. A. J. (2020) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2020.09.014 · Cited by 72
Mitochondria: An Integrative Hub Coordinating Circadian Rhythms, Metabolism, the Microbiome, and Immunity
Aguilar‐López, B. A., Moreno‐Altamirano, M. M. B., Dockrell, H. M., Duchen, M. R., & Sánchez‐García, F. J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00051 · Cited by 73
Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic‐ co ‐glycolic acid), and Silica Nanoparticles
Saborano, R., Wongpinyochit, T., Totten, J. D., Johnston, B. F., Seib, F. P., & Duarte, I. F. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201601240 · Cited by 68
Differential expression of novel metabolic and immunological biomarkers in oysters challenged with a virulent strain of OsHV-1
Young, T., Kesarcodi-Watson, A., Alfaro, A. C., Mérien, F., Nguyen, T. V., Mae, H., Le, D. V., & Villas-Bôas, S. G. (2017) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2017.03.025 · Cited by 64
Mitochondrial ACOD1/IRG1 in infection and sterile inflammation
Wu, R., Kang, R., & Tang, D. (2022) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2022.01.001 · Cited by 63
PEGylation-Dependent Metabolic Rewiring of Macrophages with Silk Fibroin Nanoparticles
Totten, J. D., Wongpinyochit, T., Carrola, J., Duarte, I. F., & Seib, F. P. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.8b18716 · Cited by 59
Distinct metabolic patterns during microglial remodeling by oleate and palmitate
Chausse, B., Kakimoto, P. A., Caldeira-da-Silva, C. C., Chaves-Filho, A. B., Yoshinaga, M. Y., da Silva, R. P., Miyamoto, S., & Kowaltowski, A. J. (2019) · Bioscience Reports · doi:10.1042/bsr20190072 · Cited by 59
Succinate in ischemia: Where does it come from?
Chinopoulos, C. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.105580 · Cited by 55
Self-citation
Control of immune cell signaling by the immuno-metabolite itaconate
Lang, R., & Siddique, M. N. A. A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1352165 · Cited by 57
Versatility of microglial bioenergetic machinery under starving conditions
Nagy, Á., Fekete, R., Horváth, G., Koncsos, G., Kriston, C., Sebestyén, A. R., Giricz, Z., Környei, Z., Madarász, E., & Tretter, L. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2017.12.002 · Cited by 53
Self-citation
Crosstalk Between Staphylococcus aureus and Innate Immunity: Focus on Immunometabolism
Horn, C. M., & Kielian, T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.621750 · Cited by 53
Multi-omics systems toxicology study of mouse lung assessing the effects of aerosols from two heat-not-burn tobacco products and cigarette smoke
Titz, B., Szostak, J., Sewer, A., Phillips, B. W., Nury, C., Schneider, T. L., Dijon, S., Lavrynenko, O., Elamin, A., Guedj, E., et al. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.04.011 · Cited by 51
HIF1α-Dependent Metabolic Signals Control the Differentiation of Follicular Helper T Cells
Dong, L., He, Y., Zhou, S., Cao, Y., Li, Y., Bi, Y., & Liu, G. (2019) · Cells · doi:10.3390/cells8111450 · Cited by 47
Metabolomic profiling of macrophages determines the discrete metabolomic signature and metabolomic interactome triggered by polarising immune stimuli
Rattigan, K. M., Pountain, A. W., Regnault, C., Achcar, F., Vincent, I. M., Goodyear, C. S., & Barrett, M. P. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194126 · Cited by 45
Porphyromonas gingivalis inhibits M2 activation of macrophages by suppressing α‐ketoglutarate production in mice
Yu, S., Ding, L., Liang, D., & Luo, L. (2018) · Molecular Oral Microbiology · doi:10.1111/omi.12241 · Cited by 45
Extracellular Vesicles From LPS-Treated Macrophages Aggravate Smooth Muscle Cell Calcification by Propagating Inflammation and Oxidative Stress
Yaker, L., Tebani, A., Lesueur, C., Dias, C., Jung, V. A., Bekri, S., Guerrera, I. C., Kamel, S., Ausseil, J., & Boullier, A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.823450 · Cited by 44
The promise and peril of targeting cell metabolism for cancer therapy
Weiss, J. M. (2019) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-019-02432-7 · Cited by 44
Spontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters
Parker, S. J., Encarnación-Rosado, J., Hollinshead, K. E. R., Hollinshead, D. M., Ash, L. J., Rossi, J. A. K., Lin, E. Y., Sohn, A. S. W., Philips, M. R., Jones, D. R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25228-9 · Cited by 43
Macrophage polarization in hypoxia and ischemia/reperfusion: Insights into the role of energetic metabolism
Yakupova, E. I., Maleev, G. V., Krivtsov, A. V., & Plotnikov, E. Y. (2022) · Experimental Biology and Medicine · doi:10.1177/15353702221080130 · Cited by 39
GABA, glutamine, glutamate oxidation and succinic semialdehyde dehydrogenase expression in human gliomas
Hujber, Z., Horváth, G., Petővári, G., Krencz, I., Dankó, T., Mészáros, K. V., Rajnai, H., Szoboszlai, N., Leenders, W. P. J., Jeney, A., et al. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0946-5 · Cited by 38
Self-citation
Itaconic acid impairs the mitochondrial function by the inhibition of complexes II and IV and induction of the permeability transition pore opening in rat liver mitochondria
Belosludtsev, K. N., Belosludtseva, N. V., Kosareva, E. A., Talanov, E. Y., Gudkov, S. V., & Dubinin, M. V. (2020) · Biochimie · doi:10.1016/j.biochi.2020.07.011 · Cited by 37
Process engineering of pH tolerant Ustilago cynodontis for efficient itaconic acid production
Tehrani, H. H., Saur, K. M., Tharmasothirajan, A., Blank, L. M., & Wierckx, N. J. P. (2019) · Microbial Cell Factories · doi:10.1186/s12934-019-1266-y · Cited by 37
Proline Oxidation Supports Mitochondrial ATP Production When Complex I Is Inhibited
Pallag, G., Nazarian, S., Ravasz, D., Bui, D., Komlódi, T., Doerrier, C., Gnaiger, E., Seyfried, T. N., & Chinopoulos, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095111 · Cited by 34
Self-citation
Selection of reliable reference genes for the normalisation of gene expression levels following time course LPS stimulation of murine bone marrow derived macrophages
Tanaka, A., To, J., O’Brien, B. A., Donnelly, S., & Lund, M. E. (2017) · BMC Immunology · doi:10.1186/s12865-017-0223-y · Cited by 33
New Avenues of Heme Synthesis Regulation
Medlock, A. E., & Dailey, H. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137467 · Cited by 33
The potential therapeutic role of itaconate and mesaconate on the detrimental effects of LPS-induced neuroinflammation in the brain
Ohm, M., Hosseini, S., Lonnemann, N., He, W., More, T. H., Goldmann, O., Medina, E., Hiller, K., & Körte, M. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03188-3 · Cited by 36
IRG1 increases MHC class I level in macrophages through STAT-TAP1 axis depending on NADPH oxidase mediated reactive oxygen species
Liu, X., Wu, X., Zhu, X., Li, T., & Liu, Y. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.04.012 · Cited by 31
Two for the price of one: itaconate and its derivatives as an anti-infective and anti-inflammatory immunometabolite
McGettrick, A. F., & O'Neill, L. A. J. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102268 · Cited by 33
Two transgenic mouse models for β-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations
Kacsó, G., Ravasz, D., Dóczi, J., Németh, B., Madgar, O., Saada, A., Ilin, P., Miller, C., Østergaard, E., Iordanov, I., et al. (2016) · Biochemical Journal · doi:10.1042/bcj20160594 · Cited by 28
Self-citation
Mycoplasma infection and hypoxia initiate succinate accumulation and release in the VM-M3 cancer cells
Flores, R. E., Brown, A. K., Taus, L. J., Khoury, J., Glover, F., Kami, K., Sarangarajan, R., Walshe, T. E., Narain, N. R., Kiebish, M. A., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2018.03.012 · Cited by 31
Self-citation
The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors
Marcero, J. R., Cox, J. E., Bergonia, H. A., Medlock, A. E., Phillips, J. D., & Dailey, H. A. (2021) · Blood Advances · doi:10.1182/bloodadvances.2021004750 · Cited by 30
Roles of Mitochondrial Respiratory Complexes during Infection
Escoll, P., Platon, L., & Buchrieser, C. (2019) · Immunometabolism · doi:10.20900/immunometab20190011 · Cited by 25
The evolutionary tug-of-war of macrophage metabolism during bacterial infection
Almeida, L., Dhillon-LaBrooy, A., & Sparwasser, T. D. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.11.002 · Cited by 25
Reprogramming immunity with itaconate: metabolic mechanisms and therapeutic perspectives
Gao, H., Ding, M., Liu, Y., Wang, Y., Zhao, S., Chen, J., Chen, Z., & Wang, G. (2025) · Inflammation Research · doi:10.1007/s00011-025-02087-4 · Cited by 33
Enhanced Expression of Catalase in Mitochondria Modulates NF-κB–Dependent Lung Inflammation through Alteration of Metabolic Activity in Macrophages
Han, W., Fessel, J. P., Sherrill, T. P., Kocurek, E. G., Yull, F. E., & Blackwell, T. S. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900820 · Cited by 25
Glutaminases as a Novel Target for SDHB-Associated Pheochromocytomas/Paragangliomas
Sarkadi, B., Meszaros, K., Krencz, I., Canu, L., Krokker, L., Zakarias, S., Barna, G., Sebestyen, A., Papay, J., Hujber, Z., et al. (2020) · Cancers · doi:10.3390/cancers12030599 · Cited by 23
Self-citation
From Glucose to Lactate and Transiting Intermediates Through Mitochondria, Bypassing Pyruvate Kinase: Considerations for Cells Exhibiting Dimeric PKM2 or Otherwise Inhibited Kinase Activity
Chinopoulos, C. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.543564 · Cited by 23
Self-citation
In vivo itaconate tracing reveals degradation pathway and turnover kinetics
Willenbockel, H. F., Williams, A. T., Lucas, A., Reynolds, M. B., Joulia, E., Ruchhoeft, M. L., Dowerg, B., Cabrales, P., Metallo, C. M., & Cordes, T. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01363-1 · Cited by 25
Basic Mechanisms of Immunometabolites in Shaping the Immune Response
Ryan, D. G., Peace, C. G., & Hooftman, A. (2023) · Journal of Innate Immunity · doi:10.1159/000535452 · Cited by 22
Mitoimmunity—when mitochondria dictates macrophage function
Corrêa‐da‐Silva, F., Pereira, J. A. D. S., de Aguiar, C. F., & Moraes‐Vieira, P. M. (2017) · Cell Biology International · doi:10.1002/cbin.10921 · Cited by 22
Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease
Sanmarco, L. M., Eberhardt, N., Bergero, G., Palacio, L. P. Q., Adami, P. V. M., Visconti, L. M., Minguez, Á. R., Hernández-Vásquez, Y., Silva, E. A. C., Morelli, L., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.123490 · Cited by 21
Itaconate or how I learned to stop avoiding the study of immunometabolism
Coelho, C. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010361 · Cited by 21
Itaconic Acid – An Emerging Building Block
Steiger, M. G., Wierckx, N. J. P., Blank, L. M., Mattanovich, D., & Sauer, M. (2016) · Industrial Biotechnology · doi:10.1002/9783527807833.ch15 · Cited by 19
Surface conjugation of poly (dimethyl siloxane) with itaconic acid-based materials for antibacterial effects
Birajdar, M. S., Cho, H., Seo, Y., Choi, J. H., & Park, H. (2017) · Applied Surface Science · doi:10.1016/j.apsusc.2017.12.125 · Cited by 18
Exploring the evolutionary roots and physiological function of itaconate
Cordes, T., & Metallo, C. M. (2020) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2020.11.005 · Cited by 18
Molecular Mechanisms of Iron Metabolism and Overload
Tayal, A., Kaur, J., Sadeghi, P., & Maitta, R. W. (2025) · Biomedicines · doi:10.3390/biomedicines13092067 · Cited by 24
Itaconate and Its Derivatives Repress Early Myogenesis In Vitro and In Vivo
Oh, T. S., Hutchins, D. C., Mainali, R., Goslen, K. H., & Quinn, M. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.748375 · Cited by 16
Tracing insights into human metabolism using chemical engineering approaches
Cordes, T., & Metallo, C. M. (2016) · Current Opinion in Chemical Engineering · doi:10.1016/j.coche.2016.08.019 · Cited by 14
IRG1/Itaconate induces metabolic reprogramming to suppress ER-positive breast cancer cell growth.
Wang, H., Chang, W., Lee, D., Li, X., & Hung, M. (2023) · PubMed Central · Cited by 11
Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue
Mikulás, K., Komlódi, T., Földes, A., Sváb, G., Horváth, G., Nagy, Á., Ambrus, A., Gyulai-Gaál, S., Gera, I., Hermann, P., et al. (2020) · Materials · doi:10.3390/ma13163472 · Cited by 11
Self-citation
The itaconate family of immunomodulators grows
McGettrick, A. F., & O'Neill, L. A. J. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00578-w · Cited by 11
Mitochondrial uncoupling caused by a wide variety of protonophores is differently sensitive to carboxyatractyloside in rat heart and liver mitochondria
Khailova, L. S., Kirsanov, R. S., Rokitskaya, T. I., Krasnov, V. S., Korshunova, G. A., Kotova, Е. А., & Antonenko, Y. N. (2024) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2024.149506 · Cited by 10
The role and therapeutic potential of itaconate in lung disease
He, R., Zuo, Y., Yi, K., Liu, B., Song, C., Li, N., & Geng, Q. (2024) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00642-1 · Cited by 11
Fungal Patterns Induce Cytokine Expression through Fluxes of Metabolic Intermediates That Support Glycolysis and Oxidative Phosphorylation
Mancebo, C., Fernández, J. J., Herrero-Sánchez, C., Álvarez, Y., Alonso, S., Sandoval, T. A., Cubillos‐Ruiz, J. R., Montero, O., Fernández, N., & Crespo, M. S. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100666 · Cited by 10
Krebs Cycle Rewired: Driver of Atherosclerosis Progression?
Liang, Y., Chen, Y., Lü, L., Zhang, S., Xiao, J., & Wei, D. (2021) · Current Medicinal Chemistry · doi:10.2174/0929867328666210806105246 · Cited by 11
Effects of a Formula with scGOS/lcFOS (9:1) and Glycomacropeptide (GMP) Supplementation on the Gut Microbiota of Very Preterm Infants
Yu, X., Xing, Y., Liu, H., Chang, Y.-M., You, Y., Dou, Y., Liu, B., Wang, Q., Ma, D., Chen, L., et al. (2022) · Nutrients · doi:10.3390/nu14091901 · Cited by 9
Glucose Metabolic Reprogramming of Macrophages Against Mycobacterium tuberculosis Infection
Liu, T., Yang, Z., Tong, J., Gao, M., & Pang, Y. (2025) · ImmunoTargets and Therapy · doi:10.2147/itt.s552746 · Cited by 9
Metabolic Adaptations and Functional Activity of Macrophages in Homeostasis and Inflammation
Yurakova, T. R., Gorshkova, E. A., Nosenko, M. A., & Drutskaya, M. S. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924050043 · Cited by 7

Authors: Németh, B., Doczi, J., Csete, D., Kacso, G., Ravasz, D., Adams, D., Kiss, G., Nagy, A. M., Horvath, G., Tretter, L., Mócsai, A., Csépáinyi‐Kömi, R., Iordanov, I., Adam‐Vizi, V., & Chinopoulos, C.
Affiliations: Department of Medical Biochemistry Semmelweis University Budapest Hungary
Department of Physiology Semmelweis University Budapest Hungary
Semmelweis University (HU)
Corresponding author: Chinopoulos, Christos
ORCID: Ravasz, Dora
Adams, Daniel
Mócsai, Attila
Iordanov, Iordan
Chinopoulos, Christos
Venue: The FASEB Journal
Publisher: Wiley
Published: 2015-09-10
Volume: 30
Issue: 1
Pages: 286-300
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.15-279398
OpenAlex: W2232390838
Cited by: 136
References: 65
Citations by year: 2026: 7 · 2025: 13 · 2024: 9 · 2023: 7 · 2022: 20 · 2021: 14 · 2020: 15 · 2019: 15 · 2018: 11 · 2017: 15 · 2016: 9 · 2015: 1
FWCI: 5.90
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
Semmelweis University Repository (Semmelweis University) (submittedVersion)
Funders: Magyar Tudományos Akadémia (02001)
Hungarian Scientific Research Fund (K 100918)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords: itaconic acid, IRG1, substrate-level phosphorylation, macrophages, LPS, complex II inhibition, succinic acid, adenine nucleotide translocase, mitochondrial bioenergetics, glycolysis, rotenone, malonate, alpha-ketoglutarate dehydrogenase complex, succinyl-CoA, ATP depletion, bone marrow-derived macrophages, RAW 264.7 macrophages
MeSH terms: Mitochondrial ADP, ATP Translocases, Animals, Cell Line, Chlorocebus aethiops, Female, Glycolysis, Hydro-Lyases, Lipopolysaccharides, Macrophages, Male, Malonates, Mice, Inbred C57BL, Mitochondria, Liver, Oxidative Phosphorylation, Rotenone, Succinates, Succinate-CoA Ligases, COS Cells, Mice, Membrane Potential, Mitochondrial

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

Abolition of mitochondrial substrate‐level phosphorylation by itaconic acid produced by LPS‐induced Irg1 expression in cells of murine macrophage lineage

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks