1932

Abstract

Itaconic acid is well known as a precursor for polymer synthesis and has been involved in industrial processes for decades. In a recent surprising discovery, itaconic acid was found to play a role as an immune-supportive metabolite in mammalian immune cells, where it is synthesized as an antimicrobial compound from the citric acid cycle intermediate -aconitic acid. Although the immune-responsive gene 1 protein (IRG1) has been associated to immune response without a mechanistic function, the critical link to itaconic acid production through an enzymatic function of this protein was only recently revealed. In this review, we highlight the history of itaconic acid as an industrial and antimicrobial compound, starting with its biotechnological synthesis and ending with its antimicrobial function in mammalian immune cells.

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2015-07-17
2024-04-19
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Literature Cited

  1. Ackermann WW, Potter VR. 1.  1949. Enzyme inhibition in relation to chemotherapy. Proc. Soc. Exp. Biol. Med. 72:11–9 [Google Scholar]
  2. Adler J, Wang S-F, Lardy HA. 2.  1957. The metabolism of itaconic acid by liver mitochondria. J. Biol. Chem. 229:2865–79 [Google Scholar]
  3. Basler T, Jeckstadt S, Valentin-Weigand P, Goethe R. 3.  2006. Mycobacterium paratuberculosis, Mycobacterium smegmatis, and lipopolysaccharide induce different transcriptional and post-transcriptional regulation of the IRG1 gene in murine macrophages. J. Leukoc. Biol. 79:3628–38 [Google Scholar]
  4. Baup S. 4.  1836. Ueber eine neue pyrogen-citronensäure, und über benennung der pyrogen-säuren überhaupt. Ann. Pharm. 19:129–38 [Google Scholar]
  5. Bentley R, Thiessen CP. 5.  1957. Biosynthesis of itaconic acid in Aspergillus terreus. III. The properties and reaction mechanism of cis-aconitic acid decarboxylase. J. Biol. Chem. 226:703–20 [Google Scholar]
  6. Bentley R, Thiessen CP. 6.  1957. Biosynthesis of itaconic acid in Aspergillus terreus. I. Tracer studies with C14-labeled substrates. J. Biol. Chem. 226:2673–87 [Google Scholar]
  7. Bercovitz A, Peleg Y, Battat E, Rokem JS, Goldberg I. 7.  1990. Localization of pyruvate carboxylase in organic acid-producing Aspergillus strains. Appl. Environ. Microbiol. 56:61594–97 [Google Scholar]
  8. Berg IA, Filatova LV, Ivanovsky RN. 8.  2002. Inhibition of acetate and propionate assimilation by itaconate via propionyl-CoA carboxylase in isocitrate lyase-negative purple bacterium Rhodospirillum rubrum. FEMS Microbiol. Lett. 216:149–54 [Google Scholar]
  9. Bonnarme P, Gillet B, Sepulchre AM, Role C, Beloeil JC, Ducrocq C. 9.  1995. Itaconate biosynthesis in Aspergillus terreus. J. Bacteriol. 177:123573–78 [Google Scholar]
  10. Booth AN, Taylor J, Wilson RH, Deeds F. 10.  1952. The inhibitory effects of itaconic acid in vitro and in vivo. J. Biol. Chem. 195:2697–702 [Google Scholar]
  11. Bressler E, Braun S. 11.  2000. Conversion of citric acid to itaconic acid in a novel liquid membrane bioreactor. J. Chem. Technol. Biotechnol. 75:166–72 [Google Scholar]
  12. Calam CT, Oxford AE, Raistrick H. 12.  1939. Studies in the biochemistry of micro-organisms: itaconic acid, a metabolic product of a strain of Aspergillus terreus Thom. Biochem. J. 33:91488–95 [Google Scholar]
  13. Chen CY, Shyu AB. 13.  1995. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem. Sci. 20:11465–70 [Google Scholar]
  14. Chen X, Tsukaguchi H, Chen XZ, Berger UV, Hediger MA. 14.  1999. Molecular and functional analysis of SDCT, a novel rat sodium-dependent dicarboxylate transporter. J. Clin. Invest. 103:81159–68 [Google Scholar]
  15. Cheng J, Che N, Li H, Ma K, Wu S. 15.  et al. 2013. Extraction, derivatization, and determination of metabolome in human macrophages. J. Sep. Sci. 36:81418–28 [Google Scholar]
  16. Cheon Y-P, Xu X, Bagchi MK, Bagchi IC. 16.  2003. Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse. Endocrinology 144:125623–30 [Google Scholar]
  17. Cho H, Proll SC, Szretter KJ, Katze MG, Gale M, Diamond MS. 17.  2013. Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses. Nat. Med. 19:4458–64 [Google Scholar]
  18. Choi S-H, Aid S, Kim H-W, Jackson SH, Bosetti F. 18.  2012. Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation. J. Neurochem. 120:2292–301 [Google Scholar]
  19. Classen A, Lloberas J, Celada A. 19.  2009. Macrophage activation: classical versus alternative. Methods Mol. Biol. 531:29–43 [Google Scholar]
  20. Cooper RA, Kornberg HL. 20.  1964. The utilization of itaconate by Pseudomonas sp. Biochem. J. 91:182–91 [Google Scholar]
  21. de Seymour JV, Conlon CA, Sulek K, Villas Bôas SG, McCowan LME. 21.  et al. 2014. Early pregnancy metabolite profiling discovers a potential biomarker for the subsequent development of gestational diabetes mellitus. Acta Diabetol. 51:5887–90 [Google Scholar]
  22. Degrandi D, Hoffmann R, Beuter-Gunia C, Pfeffer K. 22.  2009. The proinflammatory cytokine-induced IRG1 protein associates with mitochondria. J. Interferon Cytokine Res. 29:155–67 [Google Scholar]
  23. Dervartanian DV, Veeger C. 23.  1964. Studies on succinate dehydrogenase. I. Spectral properties of the purified enzyme and formation of enzyme-competitive inhibitor complexes. Biochim. Biophys. Acta 92:233–47 [Google Scholar]
  24. Dunn MF, Ramírez-Trujillo JA, Hernández-Lucas I. 24.  2009. Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis. Microbiology 155:Part 103166–75 [Google Scholar]
  25. Dwiarti L, Yamane K, Yamatani H, Kahar P, Okabe M. 25.  2002. Purification and characterization of cis-aconitic acid decarboxylase from Aspergillus terreus TN484-M1. J. Biosci. Bioeng. 94:129–33 [Google Scholar]
  26. El-Imam AA, Du C. 26.  2014. Fermentative itaconic acid production. J. Biodivers. Bioprospect. Dev. 1:11–8 [Google Scholar]
  27. Emmrich R. 27.  1939. Stoffwechselversuche mit einigen methylierten niedermolekularen dicarbonsäuren. Hoppe-Seyler's Zeitschrift für Physiol. Chemie 261:1–261–70 [Google Scholar]
  28. Fang FC, Libby SJ, Castor ME, Fung AM. 28.  2005. Isocitrate lyase (acea) is required for Salmonella persistence but not for acute lethal infection in mice. Infect. Immun. 73:42547–49 [Google Scholar]
  29. Ghassabeh GH, De Baetselier P, Brys L, Noël W, Van Ginderachter JA. 29.  et al. 2006. Identification of a common gene signature for type II cytokine-associated myeloid cells elicited in vivo in different pathologic conditions. Blood 108:2575–83 [Google Scholar]
  30. Ghesquière B, Wong BW, Kuchnio A, Carmeliet P. 30.  2014. Metabolism of stromal and immune cells in health and disease. Nature 511:7508167–76 [Google Scholar]
  31. Goncharov NV, Jenkins RO, Radilov AS. 31.  2006. Toxicology of fluoroacetate: a review, with possible directions for therapy research. J. Appl. Toxicol. 26:2148–61 [Google Scholar]
  32. Gordon S. 32.  2003. Alternative activation of macrophages. Nat. Rev. Immunol. 3:123–35 [Google Scholar]
  33. Gordon S, Martinez FO. 33.  2010. Alternative activation of macrophages: mechanism and functions. Immunity 32:5593–604 [Google Scholar]
  34. Gyamerah MH. 34.  1995. Oxygen requirement and energy relations of itaconic acid fermentation by Aspergillus terreus NRRL 1960. Appl. Microbiol. Biotechnol. 44:1–220–26 [Google Scholar]
  35. Hall CJ, Boyle RH, Astin JW, Flores MV, Oehlers SH. 35.  et al. 2013. Immunoresponsive gene 1 augments bactericidal activity of macrophage-lineage cells by regulating β-oxidation-dependent mitochondrial ROS production. Cell Metab. 18:2265–78 [Google Scholar]
  36. Hall CJ, Boyle RH, Sun X, Wicker SM, Misa JP. 36.  et al. 2014. Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production. Nat. Commun. 5:3880 [Google Scholar]
  37. Haschemi A, Kosma P, Gille L, Evans CR, Burant CF. 37.  et al. 2012. The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15:6813–26 [Google Scholar]
  38. Haskins RHR, Thorn JA, Boothroyd B. 38.  1955. Biochemistry of the Ustilaginales. XI. Metabolic products of Ustilago zeae in submerged culture. Can. J. Microbiol. 1:9749–56 [Google Scholar]
  39. Hevekerl A, Kuenz A, Vorlop K-D. 39.  2014. Filamentous fungi in microtiter plates—an easy way to optimize itaconic acid production with Aspergillus terreus. Appl. Microbiol. Biotechnol. 98:166983–89 [Google Scholar]
  40. Höner zu Bentrup K, Miczak A, Swenson DL, Russell DG. 40.  1999. Characterization of activity and expression of isocitrate lyase in mycobacterium avium and mycobacterium tuberculosis. J. Bacteriol. 181:237161–67 [Google Scholar]
  41. Hoshino K, Kaisho T, Iwabe T, Takeuchi O, Akira S. 41.  2002. Differential involvement of IFN-β in toll-like receptor-stimulated dendritic cell activation. Int. Immunol. 14:101225–31 [Google Scholar]
  42. Jaklitsch WM, Kubicek CP, Scrutton MC. 42.  1991. The subcellular organization of itaconate biosynthesis in Aspergillus terreus. J. Gen. Microbiol. 137:3533–39 [Google Scholar]
  43. Kanamasa S, Dwiarti L, Okabe M, Park EY. 43.  2008. Cloning and functional characterization of the cis-aconitic acid decarboxylase (CAD) gene from Aspergillus terreus. Appl. Microbiol. Biotechnol. 80:2223–29 [Google Scholar]
  44. Kautola H, Rymowicz W, Linko Y-Y, Linko P. 44.  1991. Itaconic acid production by immobilized Aspergillus terreus with varied metal additions. Appl. Microbiol. Biotechnol. 35:2154–58 [Google Scholar]
  45. Kekuda R, Wang H, Huang W, Pajor AM, Leibach FH. 45.  et al. 1999. Primary structure and functional characteristics of a mammalian sodium-coupled high affinity dicarboxylate transporter. J. Biol. Chem. 274:63422–29 [Google Scholar]
  46. Kinoshita K. 46.  1931. Über eine neue Aspergillus-Art, Asp. itaconicus nov. spec. Bot. Mag. Tokyo 45:45–50 [Google Scholar]
  47. Klement T, Büchs J. 47.  2013. Itaconic acid—a biotechnological process in change. Bioresour. Technol. 135:422–31 [Google Scholar]
  48. Knowles RG, Moncada S. 48.  1994. Nitric oxide synthases in mammals. Biochem. J. 298:Part 2249–58 [Google Scholar]
  49. Kominsky DJ, Campbell EL, Colgan SP. 49.  2010. Metabolic shifts in immunity and inflammation. J. Immunol. 184:84062–68 [Google Scholar]
  50. Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E. 50.  et al. 2010. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115:234742–49 [Google Scholar]
  51. Kumar R. 51.  2009. Glyoxylate shunt: combating mycobacterium at forefront. Int. J. Integr. Biol. 7:269–72 [Google Scholar]
  52. Larsen BYH, Eimhjellen KE. 52.  1954. The mechanism of itaconic acid formation by Aspergillus terreus. 1. The effect of acidity. Biochem. J. 6:135–39 [Google Scholar]
  53. Lee Jenkins NA, Gilbert DJ, Copeland NG, O'Brien WE. 53.  1995. Cloning and analysis of gene regulation of a novel LPS-inducible cDNA. Immunogenetics 41:5263–70 [Google Scholar]
  54. Li H, Gang Z, Yuling H, Luokun X, Jie X. 54.  et al. 2006. Different neurotropic pathogens elicit neurotoxic CCR9- or neurosupportive CXCR3-expressing microglia. J. Immunol. 177:63644–56 [Google Scholar]
  55. Li Y, Zhang P, Wang C, Han C, Meng J. 55.  et al. 2013. Immune responsive gene 1 (IRG1) promotes endotoxin tolerance by increasing A20 expression in macrophages through ROS. J. Biol. Chem. 1:2316225–34 [Google Scholar]
  56. Lin Y-H, Li Y-F, Huang M-C, Tsai Y-C. 56.  2004. Intracellular expression of vitreoscilla hemoglobin in Aspergillus terreus to alleviate the effect of a short break in aeration during culture. Biotechnol. Lett. 26:131067–72 [Google Scholar]
  57. Maassen N, Panakova M, Wierckx N, Geiser E, Zimmermann M. 57.  et al. 2014. Influence of carbon and nitrogen concentration on itaconic acid production by the smut fungus Ustilago maydis. Eng. Life Sci. 14:2129–34 [Google Scholar]
  58. Martin WR, Frigan F, Bergman EEH. 58.  1961. Noninductive metabolism of itaconic acid by Pseudomonas and Salmonella species. J. Bacteriol. 82:6905–8 [Google Scholar]
  59. McFadden BA, Purohit S. 59.  1977. Itaconate, an isocitrate lyase-directed inhibitor in Pseudomonas indigofera. J. Bacteriol. 131:1136–44 [Google Scholar]
  60. McFadden BA, Williams JO, Roche TE. 60.  1971. Mechanism of action of isocitrate lyase from Pseudomonas indigofera. Biochemistry 10:81384–90 [Google Scholar]
  61. McKinney JD, Höner zu Bentrup K, Muñoz-Elías EJ, Miczak A, Chen B. 61.  et al. 2000. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406:6797735–38 [Google Scholar]
  62. Meissner F, Scheltema RA, Mollenkopf H-J, Mann M. 62.  2013. Direct proteomic quantification of the secretome of activated immune cells. Science 340:6131475–78 [Google Scholar]
  63. Ménage S, Attrée I. 63.  2014. Pathogens love the poison. Nat. Chem. Biol. 10:5326–27 [Google Scholar]
  64. Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N. 64.  et al. 2013. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. PNAS 110:197820–25 [Google Scholar]
  65. Mills E, O'Neill LAJ. 65.  2014. Succinate: a metabolic signal in inflammation. Trends Cell Biol. 24:5313–20 [Google Scholar]
  66. Mor G, Cardenas I, Abrahams V, Guller S. 66.  2011. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann. N. Y. Acad. Sci. 1221:80–87 [Google Scholar]
  67. Mosser DM. 67.  2003. The many faces of macrophage activation. J. Leukoc. Biol. 73:2209–12 [Google Scholar]
  68. Muñoz-Elias EJ. 68.  2006. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat. Med. 11:6638–44 [Google Scholar]
  69. Muñoz-Elías EJ, McKinney JD. 69.  2006. Carbon metabolism of intracellular bacteria. Cell. Microbiol. 8:110–22 [Google Scholar]
  70. Nelson KK, Melendez JA. 70.  2004. Mitochondrial redox control of matrix metalloproteinases. Free Radic. Biol. Med. 37:6768–84 [Google Scholar]
  71. O'Neill LAJ, Hardie DG. 71.  2013. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493:7432346–55 [Google Scholar]
  72. Okabe M, Lies D, Kanamasa S, Park EY. 72.  2009. Biotechnological production of itaconic acid and its biosynthesis in Aspergillus terreus. Appl. Microbiol. Biotechnol. 84:4597–606 [Google Scholar]
  73. Okabe M, Ohta N, Park YS. 73.  1993. Itaconic acid production in an air-lift bioreactor using a modified draft tube. J. Ferment. Bioeng. 76:2117–22 [Google Scholar]
  74. Pandey AK, Sassetti CM. 74.  2008. Mycobacterial persistence requires the utilization of host cholesterol. PNAS 105:114376–80 [Google Scholar]
  75. Patel TR, McFadden BA. 75.  1978. Caenorhabditis elegans and Ascaris suum: inhibition of isocitrate lyase by itaconate. Exp. Parasitol. 44:2262–68 [Google Scholar]
  76. Pearce EL, Pearce EJ. 76.  2013. Metabolic pathways in immune cell activation and quiescence. Immunity 38:4633–43 [Google Scholar]
  77. Preusse M, Tantawy MA, Klawonn F, Schughart K, Pessler F. 77.  2013. Infection- and procedure-dependent effects on pulmonary gene expression in the early phase of influenza A virus infection in mice. BMC Microbiol. 13:293 [Google Scholar]
  78. Rodríguez-Prados J-C, Través PG, Cuenca J, Rico D, Aragonés J. 78.  et al. 2010. Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J. Immunol. 185:1605–14 [Google Scholar]
  79. Russell DG, Vanderven BC, Lee W, Abramovitch RB, Homolka S. 79.  et al. 2010. Mycobacterium tuberculosis wears what it eats. Cell Host Microbe 8:168–76 [Google Scholar]
  80. Sakai A, Kusumoto A, Kiso Y, Furuya E. 80.  2004. Itaconate reduces visceral fat by inhibiting fructose 2,6-bisphosphate synthesis in rat liver. Nutrition 20:11–12997–1002 [Google Scholar]
  81. Sasikaran J, Ziemski M, Zadora PK, Fleig A, Berg IA. 81.  2014. Bacterial itaconate degradation promotes pathogenicity. Nat. Chem. Biol. 10:371–77 [Google Scholar]
  82. Schiavone N, Rosini P, Quattrone A, Donnini M, Lapucci A. 82.  et al. 2000. A conserved AU-rich element in the 3′ untranslated region of bcl-2 mRNA is endowed with a destabilizing function that is involved in bcl-2 down-regulation during apoptosis. FASEB J. 14:1174–84 [Google Scholar]
  83. Sena LA, Chandel NS. 83.  2012. Physiological roles of mitochondrial reactive oxygen species. Mol. Cell 48:2158–67 [Google Scholar]
  84. Sharma V, Sharma S, Hoener K, McKinney JD, Russell DG. 84.  et al. 2000. Structure of isocitrate lyase, Mycobacterium tuberculosis. Nat. Struct. Biol. 7:8663–68 [Google Scholar]
  85. Shi S, Blumenthal A, Hickey CM, Gandotra S, Levy D, Ehrt S. 85.  2005. Expression of many immunologically important genes in Mycobacterium tuberculosis-infected macrophages is independent of both TLR2 and TLR4 but dependent on IFN-αβ receptor and STAT1. J. Immunol. 175:53318–28 [Google Scholar]
  86. Shin J-H, Yang J-Y, Jeon B-Y, Yoon Y-JJ, Cho S-N. 86.  et al. 2011. 1H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis. J. Proteome Res. 10:52238–47 [Google Scholar]
  87. Smith J, Sadeyen J-R, Paton IR, Hocking PM, Salmon N. 87.  et al. 2011. Systems analysis of immune responses in Marek's disease virus-infected chickens identifies a gene involved in susceptibility and highlights a possible novel pathogenicity mechanism. J. Virol. 85:2111146–58 [Google Scholar]
  88. Steiger MG, Blumhoff ML, Mattanovich D, Sauer M. 88.  2013. Biochemistry of microbial itaconic acid production. Front. Microbiol. 4:23 [Google Scholar]
  89. Strelko CL, Lu W, Dufort FJ, Seyfried TN, Chiles TC. 89.  et al. 2011. Itaconic acid is a mammalian metabolite induced during macrophage activation. J. Am. Chem. Soc. 133:4116386–89 [Google Scholar]
  90. Strelkov S, von Elstermann M, Schomburg D. 90.  2004. Comprehensive analysis of metabolites in Corynebacterium glutamicum by gas chromatography/mass spectrometry. Biol. Chem. 385:9853–61 [Google Scholar]
  91. Sugimoto M, Sakagami H, Yokote Y, Onuma H, Kaneko M. 91.  et al. 2011. Non-targeted metabolite profiling in activated macrophage secretion. Metabolomics 8:4624–33 [Google Scholar]
  92. Svineng G, Ravuri C, Rikardsen O, Huseby N-E, Winberg J-O. 92.  2008. The role of reactive oxygen species in integrin and matrix metalloproteinase expression and function. Connect. Tissue Res. 49:3197–202 [Google Scholar]
  93. Tabuchi T, Sigisawa T, Ishidori T, Nakahara T, Sugiyama J. 93.  1981. Itaconic acid fermentation by a yeast belonging to the genus Candida. Agric. Biol. Chem. 45:2475–79 [Google Scholar]
  94. Tanaka Y, Adams DH, Shaw S. 94.  1993. Proteoglycans on endothelial cells present adhesion-inducing cytokines to leukocytes. Immunol. Today 14:3111–15 [Google Scholar]
  95. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF. 95.  et al. 2013. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496:7444238–42 [Google Scholar]
  96. Terakawa J, Wakitani S, Sugiyama M, Inoue N, Ohmori Y. 96.  et al. 2011. Embryo implantation is blocked by intraperitoneal injection with anti-LIF antibody in mice. J. Reprod. Dev. 57:6700–7 [Google Scholar]
  97. Thomas DM, Francescutti-Verbeem DM, Kuhn DM. 97.  2006. Gene expression profile of activated microglia under conditions associated with dopamine neuronal damage. FASEB J. 20:3515–17 [Google Scholar]
  98. Turner E. 98.  1840. Elements of Chemistry: Including the Recent Discoveries and Doctrines of the Science Philadelphia: Cowperthwait & Co.
  99. Upton AM, McKinney JD. 99.  2007. Role of the methylcitrate cycle in propionate metabolism and detoxification in Mycobacterium smegmatis. Microbiology 153:Part 123973–82 [Google Scholar]
  100. Van der Geize R, Yam K, Heuser T, Wilbrink MH, Hara H. 100.  et al. 2007. A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into Mycobacterium tuberculosis survival in macrophages. PNAS 104:61947–52 [Google Scholar]
  101. Van der Straat L, Vernooij M, Lammers M, van den Berg W, Schonewille T. 101.  et al. 2014. Expression of the Aspergillus terreus itaconic acid biosynthesis cluster in Aspergillus niger. Microb. Cell Fact. 13:111 [Google Scholar]
  102. Van Schaik EJ, Tom M, Woods DE. 102.  2009. Burkholderia pseudomallei isocitrate lyase is a persistence factor in pulmonary melioidosis: implications for the development of isocitrate lyase inhibitors as novel antimicrobials. Infect. Immun. 77:104275–83 [Google Scholar]
  103. Vander Heiden MG, Cantley LC, Thompson CB. 103.  2009. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:59301029–33 [Google Scholar]
  104. Wang SF, Adler J, Lardy HA. 104.  1961. The pathway of itaconate metabolism by liver mitochondria. J. Biol. Chem. 236:26–30 [Google Scholar]
  105. West AP, Brodsky IE, Rahner C, Woo DK, Erdjument-Bromage H. 105.  et al. 2011. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472:7344476–80 [Google Scholar]
  106. Willke T, Vorlop KD. 106.  2001. Biotechnological production of itaconic acid. Appl. Microbiol. Biotechnol. 56:3–4289–95 [Google Scholar]
  107. Xiao W, Wang L, Xiao R, Wu M, Tan J, He Y. 107.  2011. Expression profile of human immune-responsive gene 1 and generation and characterization of polyclonal antiserum. Mol. Cell Biochem. 353:1–2177–87 [Google Scholar]
  108. Yahiro K, Takahama T, Jai S, Park Y, Okabe M. 108.  1997. Comparison of air-lift and stirred tank reactors for itaconic acid production by Aspergillus terreus. Biotechnol. Lett. 19:7619–21 [Google Scholar]
  109. Yahiro K, Takahama T, Park YS, Okabe M. 109.  1995. Breeding of Aspergillus terreus mutant TN-484 for itaconic acid production with high yield. J. Ferment. Bioeng. 79:5506–8 [Google Scholar]
  110. Zinchenko VP, Goncharov NV, Teplova VV, Kasymov VA, Petrova OI. 110.  et al. 2007. Interaction of intracellular signalling and metabolic pathways at inhibition of mitochondrial aconitase by fluoroacetate. Cell Tissue Biol. 1:6541–50 [Google Scholar]
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