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Gene Review

Aco2  -  aconitase 2, mitochondrial

Mus musculus

Synonyms: Aco-2, Aco3, Aconitase, Aconitate hydratase, mitochondrial, Citrate hydro-lyase, ...
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Disease relevance of Aco2


Psychiatry related information on Aco2


High impact information on Aco2

  • Cytochemical analysis revealed a severe reduction in succinate dehydrogenase (complex II) and aconitase (a TCA cycle enzyme) activities in the heart and, to a lesser extent, in other organs [8].
  • Previous studies have shown that cytotoxic activated macrophages cause inhibition of DNA synthesis, of mitochondrial respiration, and of aconitase activity in tumor target cells [9].
  • The results show that removal of a labile iron atom from the [4Fe-4S] cluster, by a cytotoxic activated macrophage-mediated mechanism, is causally related to aconitase inhibition [10].
  • Here we examine aconitase, a citric acid cycle enzyme with a catalytically active iron-sulfur cluster, to determine if iron-sulfur clusters are targets for activated macrophage-induced iron removal [10].
  • Furthermore, incubation of injured target cells in medium supplemented with ferrous ion plus a reducing agent causes near-complete reconstitution of aconitase activity [10].

Chemical compound and disease context of Aco2


Biological context of Aco2

  • Some of these measures provided evidence for an increase in oxidative stress in the mutant mice (aconitase activity, oxidized glutathione, and lipid peroxides), but others did not (superoxide dismutase, protein thiol content, carbonyl protein content, total glutathione, glutathione peroxidase, catalase, and thiobarbituric reducing substances) [11].
  • IRP1 registers cytosolic iron status mainly through an iron-sulfur switch mechanism, alternating between an active cytosolic aconitase form with an iron-sulfur cluster ligated to its active site and an apoprotein form that binds IREs [12].
  • These cells have increased oxidative metabolism, as shown by concurrent increases in aconitase activity, mitochondrial membrane potential, cellular respiration, and ATP content [13].
  • Furthermore, UV cross-linking studies indicate that highly purified mitochondrial aconitase binds specifically to the MHV 3' protein-binding element [2].
  • SOD2 null mice develop a severe neurological phenotype that includes behavioral defects, a severe spongiform encephalopathy, and a decrease in mitochondrial aconitase activity [14].

Anatomical context of Aco2

  • The susceptibility of KGDHC and aconitase to inactivation in kidney cells exposed to cisplatin metabolites may be due to the proximity of mitAspAT to KGDHC and aconitase in mitochondria [15].
  • Mitochondria-free cytosols were then prepared and aconitase activity as well as IRE binding activity and induction of IRE binding activity were correlated and depended on NO synthesis after IFN-gamma and/or LPS stimulation [16].
  • Biochemical analysis of R6/2 mouse brain at 12 weeks demonstrated a significant reduction in aconitase and mitochondrial complex IV activities in the striatum and a decrease in complex IV activity in the cerebral cortex [6].
  • Administration of MPTP in mice resulted in inactivation of mitochondrial aconitase, but not fumarase in the substantia nigra [3].
  • Interleukin-1 beta induces nitric oxide production and inhibits the activity of aconitase without decreasing glucose oxidation rates in isolated mouse pancreatic islets [17].

Associations of Aco2 with chemical compounds

  • Aconitase activity was diminished in both cell types, but only at the higher level of exposure to cisplatin [15].
  • The resulting peptide mass spectrum was compared with the Mascot and Protein Prospector databases and resulted in the specific identification of heart mitochondrial proteins, specifically Mn-superoxide dismutase (SOD), aconitase (ACN), and malate dehydrogenase (MDH) [18].
  • Authentic NO gas as well as the NO-generating compound 3-morpholinosydnonimine (SIN-1) also conversely modulated aconitase and IRE binding activities of purified recombinant IRF [16].
  • Neither the addition of a bolus of ONOO- or H2O2 nor O2-. generation significantly affected IRE binding even though they inhibited its aconitase activity [19].
  • Replacement of any or all of these cysteine residues results in a complete loss of aconitase activity [20].

Other interactions of Aco2


  1. Failure of tumor necrosis factor and interleukin-1 to elicit superoxide production in the mitochondrial matrices of mammalian cells. Gardner, P.R., White, C.W. Arch. Biochem. Biophys. (1996) [Pubmed]
  2. Mitochondrial aconitase binds to the 3' untranslated region of the mouse hepatitis virus genome. Nanda, S.K., Leibowitz, J.L. J. Virol. (2001) [Pubmed]
  3. Iron-sulfur enzyme mediated mitochondrial superoxide toxicity in experimental Parkinson's disease. Liang, L.P., Patel, M. J. Neurochem. (2004) [Pubmed]
  4. Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19. Van Greevenbroek, M.M., Vermeulen, V.M., De Bruin, T.W. J. Lipid Res. (2004) [Pubmed]
  5. Changes induced by Ehrlich ascites carcinoma in hepatic fumarase and aconitase activities. Abreu, L.A., Abreu, R.R. Experientia (1978) [Pubmed]
  6. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Tabrizi, S.J., Workman, J., Hart, P.E., Mangiarini, L., Mahal, A., Bates, G., Cooper, J.M., Schapira, A.H. Ann. Neurol. (2000) [Pubmed]
  7. Mitochondrial enzymes in schizophrenia. Bubber, P., Tang, J., Haroutunian, V., Xu, H., Davis, K.L., Blass, J.P., Gibson, G.E. J. Mol. Neurosci. (2004) [Pubmed]
  8. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Li, Y., Huang, T.T., Carlson, E.J., Melov, S., Ursell, P.C., Olson, J.L., Noble, L.J., Yoshimura, M.P., Berger, C., Chan, P.H., Wallace, D.C., Epstein, C.J. Nat. Genet. (1995) [Pubmed]
  9. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Hibbs, J.B., Taintor, R.R., Vavrin, Z. Science (1987) [Pubmed]
  10. Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. Drapier, J.C., Hibbs, J.B. J. Clin. Invest. (1986) [Pubmed]
  11. Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease. Visser, J.E., Smith, D.W., Moy, S.S., Breese, G.R., Friedmann, T., Rothstein, J.D., Jinnah, H.A. Brain Res. Dev. Brain Res. (2002) [Pubmed]
  12. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Rouault, T.A. Nat. Chem. Biol. (2006) [Pubmed]
  13. Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited. Schulz, T.J., Thierbach, R., Voigt, A., Drewes, G., Mietzner, B., Steinberg, P., Pfeiffer, A.F., Ristow, M. J. Biol. Chem. (2006) [Pubmed]
  14. Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. Hinerfeld, D., Traini, M.D., Weinberger, R.P., Cochran, B., Doctrow, S.R., Harry, J., Melov, S. J. Neurochem. (2004) [Pubmed]
  15. Cisplatin-induced toxicity is associated with platinum deposition in mouse kidney mitochondria in vivo and with selective inactivation of the alpha-ketoglutarate dehydrogenase complex in LLC-PK1 cells. Zhang, L., Cooper, A.J., Krasnikov, B.F., Xu, H., Bubber, P., Pinto, J.T., Gibson, G.E., Hanigan, M.H. Biochemistry (2006) [Pubmed]
  16. Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. Drapier, J.C., Hirling, H., Wietzerbin, J., Kaldy, P., Kühn, L.C. EMBO J. (1993) [Pubmed]
  17. Interleukin-1 beta induces nitric oxide production and inhibits the activity of aconitase without decreasing glucose oxidation rates in isolated mouse pancreatic islets. Welsh, N., Sandler, S. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  18. Association of calcineurin with mitochondrial proteins. Tokheim, A.M., Martin, B.L. Proteins (2006) [Pubmed]
  19. Modulation of iron regulatory protein functions. Further insights into the role of nitrogen- and oxygen-derived reactive species. Bouton, C., Raveau, M., Drapier, J.C. J. Biol. Chem. (1996) [Pubmed]
  20. Modification of a free Fe-S cluster cysteine residue in the active iron-responsive element-binding protein prevents RNA binding. Philpott, C.C., Haile, D., Rouault, T.A., Klausner, R.D. J. Biol. Chem. (1993) [Pubmed]
  21. Complex III releases superoxide to both sides of the inner mitochondrial membrane. Muller, F.L., Liu, Y., Van Remmen, H. J. Biol. Chem. (2004) [Pubmed]
  22. Production and characterization of monoclonal antibodies specific for Shewanella colwelliana exopolysaccharide. Sledjeski, D.D., Weiner, R.M. Appl. Environ. Microbiol. (1993) [Pubmed]
  23. Isoenzyme analysis of Hammondia hammondi and Toxoplasma gondii sporozoites. Dardé, M.L., Riahi, H., Bouteille, B., Pestre-Alexandre, M. J. Parasitol. (1992) [Pubmed]
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