Table of Contents Author Guidelines Submit a Manuscript
International Journal of Cell Biology
Volume 2012, Article ID 273947, 12 pages
http://dx.doi.org/10.1155/2012/273947
Review Article

The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells

Department of Membrane Transport Biophysics (No. 75), Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220 Prague, Czech Republic

Received 16 January 2012; Accepted 19 March 2012

Academic Editor: Juan P. Bolaños

Copyright © 2012 Katarína Smolková and Petr Ježek. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Smolková, L. Plecitá-Hlavatá, N. Bellance, G. Benard, R. Rossignol, and P. Ježek, “Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells,” International Journal of Biochemistry and Cell Biology, vol. 43, no. 7, pp. 950–968, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. A. R. Mullen, W. W. Wheaton, E. S. Jin et al., “Reductive carboxylation supports growth in tumour cells with defective mitochondria,” Nature, vol. 481, no. 7381, pp. 385–388, 2011. View at Google Scholar
  3. M. Yuneva, “Finding an “Achilles' heel” of cancer: the role of glucose and glutamine metabolism in the survival of transformed cells,” Cell Cycle, vol. 7, no. 14, pp. 2083–2089, 2008. View at Google Scholar · View at Scopus
  4. R. J. DeBerardinis and T. Cheng, “Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer,” Oncogene, vol. 29, no. 3, pp. 313–324, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. B. Nadege, L. Patrick, and R. Rodrigue, “Mitochondria: from bioenergetics to the metabolic regulation of carcinogenesis,” Frontiers in Bioscience, vol. 14, no. 11, pp. 4015–4034, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. N. C. Denko, “Hypoxia, HIF1 and glucose metabolism in the solid tumour,” Nature Reviews Cancer, vol. 8, no. 9, pp. 705–713, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Ježek, L. Plecitá-Hlavatá, K. Smolková, and R. Rossignol, “Distinctions and similarities of cell bioenergetics and the role of mitochondria in hypoxia, cancer, and embryonic development,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 5, pp. 604–622, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. R. J. Shaw, “Glucose metabolism and cancer,” Current Opinion in Cell Biology, vol. 18, no. 6, pp. 598–608, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. R. J. DeBerardinis, J. J. Lum, G. Hatzivassiliou, and C. B. Thompson, “The biology of cancer: metabolic reprogramming fuels cell growth and proliferation,” Cell Metabolism, vol. 7, no. 1, pp. 11–20, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Yuneva, N. Zamboni, P. Oefner, R. Sachidanandam, and Y. Lazebnik, “Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells,” Journal of Cell Biology, vol. 178, no. 1, pp. 93–105, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. T. Cheng, J. Sudderth, C. Yang et al., “Pyruvate carboxylase is required for glutamine-independent growth of tumor cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 21, pp. 8674–8679, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Gao, I. Tchernyshyov, T. C. Chang et al., “C-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism,” Nature, vol. 458, no. 7239, pp. 762–765, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. D. R. Wise, R. J. DeBerardinis, A. Mancuso et al., “Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 48, pp. 18782–18787, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. R. J. DeBerardinis, A. Mancuso, E. Daikhin et al., “Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19345–19350, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. R. W. Moreadith and A. L. Lehninger, “The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme,” The Journal of Biological Chemistry, vol. 259, no. 10, pp. 6215–6221, 1984. View at Google Scholar · View at Scopus
  16. R. W. Moreadith and A. L. Lehninger, “Purification, kinetic behavior, and regulation of NAD(P)+ malic enzyme of tumor mitochondria,” The Journal of Biological Chemistry, vol. 259, no. 10, pp. 6222–6227, 1984. View at Google Scholar · View at Scopus
  17. M. Israël and L. Schwartz, “The metabolic advantage of tumor cells,” Molecular Cancer, vol. 10, article 70, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Flavin, S. Peluso, P. L. Nguyen, and M. Loda, “Fatty acid synthase as a potential therapeutic target in cancer,” Future Oncology, vol. 6, no. 4, pp. 551–562, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. J. A. Menendez, “Fine-tuning the lipogenic/lipolytic balance to optimize the metabolic requirements of cancer cell growth: molecular mechanisms and therapeutic perspectives,” Biochimica et Biophysica Acta, vol. 1801, no. 3, pp. 381–391, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. L. J. Reitzer, B. M. Wice, and D. Kennell, “Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells,” The Journal of Biological Chemistry, vol. 254, no. 8, pp. 2669–2676, 1979. View at Google Scholar · View at Scopus
  21. A. L. Holleran, D. A. Briscoe, G. Fiskum, and J. K. Kelleher, “Glutamine metabolism in AS-30D hepatoma cells. Evidence for its conversion into lipids via reductive carboxylation,” Molecular and Cellular Biochemistry, vol. 152, no. 2, pp. 95–101, 1995. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Yoo, M. R. Antoniewicz, G. Stephanopoulos, and J. K. Kelleher, “Quantifying reductive carboxylation flux of glutamine to lipid in a brown adipocyte cell line,” The Journal of Biological Chemistry, vol. 283, no. 30, pp. 20621–20627, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. P. S. Ward, J. Patel, D. R. Wise et al., “The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate,” Cancer Cell, vol. 17, no. 3, pp. 225–234, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. S. P. Albracht, A. J. Meijer, and J. Rydström, “Mammalian NADH:ubiquinone oxidoreductase (Complex I) and nicotinamide nucleotide transhydrogenase (Nnt) together regulate the mitochondrial production of H2O2—implications for their role in disease, especially cancer,” Journal of Bioenergetics and Biomembranes, vol. 43, no. 5, pp. 541–564, 2011. View at Google Scholar
  25. R. M. Denton, “Regulation of mitochondrial dehydrogenases by calcium ions,” Biochimica et Biophysica Acta, vol. 1787, no. 11, pp. 1309–1316, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. Z. J. Reitman and H. Yan, “Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism,” Journal of the National Cancer Institute, vol. 102, no. 13, pp. 932–941, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. L. Dang, S. Jin, and S. M. Su, “IDH mutations in glioma and acute myeloid leukemia,” Trends in Molecular Medicine, vol. 16, no. 9, pp. 392–397, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. M. F. Amary, K. Bacsi, F. Maggiani et al., “IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours,” Journal of Pathology, vol. 224, no. 3, pp. 334–343, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. D. Capper, M. Simon, C. D. Langhans et al., “2-Hydroxyglutarate concentration in serum from patients with gliomas does not correlate with IDH1/2 mutation status or tumor size,” International Journal of Cancer. In press. View at Publisher · View at Google Scholar
  30. F. Ducray, Y. Marie, and M. Sanson, “IDH1 and IDH2 mutations in gliomas,” The New England Journal of Medicine, vol. 360, no. 21, pp. 2248–2249, 2009. View at Google Scholar
  31. C. Guo, C. J. Pirozzi, G. Y. Lopez, and H. Yan, “Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target,” Current Opinion in Neurology, vol. 24, no. 6, pp. 648–652, 2011. View at Google Scholar
  32. C. Horbinski, L. Kelly, Y. E. Nikiforov, M. B. Durso, and M. N. Nikiforova, “Detection of IDH1 and IDH2 mutations by fluorescence melting curve analysis as a diagnostic tool for brain biopsies,” Journal of Molecular Diagnostics, vol. 12, no. 4, pp. 487–492, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. D. Krell, M. Assoku, M. Galloway, P. Mulholland, I. Tomlinson, and C. Bardella, “Screen for IDH1, IDH2, IDH3, D2HGDH and l2HGDH mutations in glioblastoma,” PLoS One, vol. 6, no. 5, Article ID e19868, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Mellai, A. Piazzi, V. Caldera et al., “IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors,” Journal of Neurooncology, vol. 105, no. 2, pp. 345–357, 2011. View at Google Scholar
  35. Z. J. Reitman, G. Jin, E. D. Karoly et al., “Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 8, pp. 3270–3275, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. P. S. Ward, J. R. Cross, C. Lu et al., “Identification of additional IDH mutations associated with oncometabolite R(-)-2-hydroxyglutarate production,” Oncogene. In press. View at Publisher · View at Google Scholar
  37. H. Yan, D. W. Parsons, G. Jin et al., “IDH1 and IDH2 mutations in gliomas,” The New England Journal of Medicine, vol. 360, no. 8, pp. 765–773, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. S. Gross, R. A. Cairns, M. D. Minden et al., “Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations,” Journal of Experimental Medicine, vol. 207, no. 2, pp. 339–344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. G. Jin, Z. J. Reitman, I. Spasojevic et al., “2-hydroxyglutarate production, but not dominant negative function, is conferred by glioma-derived NADP+-dependent isocitrate dehydrogenase mutations,” PLoS One, vol. 6, no. 2, Article ID e16812, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. W. Xu, H. Yang, Y. Liu et al., “Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases,” Cancer Cell, vol. 19, no. 1, pp. 17–30, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. D. R. Wise, P. S. Ward, and J. E. Shay, “Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability,” Proceedings of the National Academy of Sciences USA, vol. 108, no. 49, pp. 19611–19616, 2011. View at Google Scholar
  42. C. V. Pereira, M. Lebiedzinsk, M. R. Wieckowski, and P. J. Oliveira, “Regulation and protection of mitochondrial physiology by sirtuins,” Mitochondrion, vol. 12, no. 1, pp. 66–76, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. M. N. Sack, “Emerging characterization of the role of SIRT3 mediated mitochondrial protein deacetylation in the heart,” American Journal of Physiology, vol. 301, no. 6, pp. H2191–H2197, 2011. View at Google Scholar
  44. S. Someya, W. Yu, W. C. Hallows et al., “Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under Caloric Restriction,” Cell, vol. 143, no. 5, pp. 802–812, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. S. H. Jo, M. K. Son, H. J. Koh et al., “Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent Isocitrate Dehydrogenase,” The Journal of Biological Chemistry, vol. 276, no. 19, pp. 16168–16176, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. S. K. In and J. W. Park, “Regulation of mitochondrial NADP+-dependent isocitrate dehydrogenase activity by glutathionylation,” The Journal of Biological Chemistry, vol. 280, no. 11, pp. 10846–10854, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. C. M. Haraguchi, T. Mabuchi, and S. Yokota, “Localization of a mitochondrial type of NADP-dependent isocitrate dehydrogenase in kidney and heart of rat: an immunocytochemical and biochemical study,” Journal of Histochemistry and Cytochemistry, vol. 51, no. 2, pp. 215–226, 2003. View at Google Scholar · View at Scopus
  48. I. U. Oh, J. Inazawa, Y. O. Kim, B. J. Song, and T. L. Huh, “Assignment of the human mitochondrial NADP+-specific isocitrate dehydrogenase (IDH2) gene to 15q26.1 by in situ hybridization,” Genomics, vol. 38, no. 1, pp. 104–106, 1996. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Minich, S. Yokota, and R. Dringen, “Cytosolic and mitochondrial isoforms of NADP+-dependent isocitrate dehydrogenases are expressed in cultured rat neurons, astrocytes, oligodendrocytes and microglial cells,” Journal of Neurochemistry, vol. 86, no. 3, pp. 605–614, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. C. Ceccarelli, N. B. Grodsky, N. Ariyaratne, R. F. Colman, and B. J. Bahnson, “Crystal structure of porcine mitochondrial NADP+-dependent isocitrate dehydrogenase complexed with Mn2+ and isocitrate: insights into the enzyme mechanism,” The Journal of Biological Chemistry, vol. 277, no. 45, pp. 43454–43462, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Soundar, B. L. Danek, and R. F. Colman, “Identification by mutagenesis of arginines in the substrate binding site of the porcine NADP-dependent isocitrate dehydrogenase,” The Journal of Biological Chemistry, vol. 275, no. 8, pp. 5606–5612, 2000. View at Publisher · View at Google Scholar · View at Scopus
  52. R. F. Colman, “Distances among coenzyme and metal Sites of NADP+-dependent isocitrate dehydrogenase using resonance energy transfer,” Biochemistry, vol. 26, no. 15, pp. 4893–4900, 1987. View at Google Scholar · View at Scopus
  53. Y. C. Huang and R. F. Colman, “Location of the coenzyme binding site in the porcine mitochondrial NADP-dependent isocitrate dehydrogenase,” The Journal of Biological Chemistry, vol. 280, no. 34, pp. 30349–30353, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Lee and R. F. Colman, “Thr373, Asp375, and Lys260 are in the coenzyme site of porcine NADP-dependent isocitrate dehydrogenase,” Archives of Biochemistry and Biophysics, vol. 450, no. 2, pp. 183–190, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Soundar, M. O'hagan, K. S. Fomulu, R. F. Colman, A. M. Tokheim, and B. L. Martin, “Association of calcineurin with mitochondrial proteins,” Proteins, vol. 64, no. 1, pp. 28–33, 2006. View at Google Scholar
  56. X. Xu, J. Zhao, Z. Xu et al., “Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity,” The Journal of Biological Chemistry, vol. 279, no. 32, pp. 33946–33957, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Green and P. Beer, “Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms,” The New England Journal of Medicine, vol. 362, no. 4, pp. 369–370, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Zhao, Y. Lin, W. Xu et al., “Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α,” Science, vol. 324, no. 5924, pp. 261–265, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. C. A. Chrestensen, D. W. Starke, and J. J. Mieyal, “Acute cadmium exposure inactivates thioltransferase (Glutaredoxin), inhibits intracellular reduction of protein-glutathionyl-mixed disulfides, and initiates apoptosis,” The Journal of Biological Chemistry, vol. 275, no. 34, pp. 26556–26565, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. S. C. Kim, R. Sprung, Y. Chen et al., “Substrate and functional diversity of lysine acetylation revealed by a proteomics survey,” Molecular Cell, vol. 23, no. 4, pp. 607–618, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Zhao, W. Xu, W. Jiang et al., “Regulation of cellular metabolism by protein lysine acetylation,” Science, vol. 327, no. 5968, pp. 1000–1004, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Schlicker, M. Gertz, P. Papatheodorou, B. Kachholz, C. F. W. Becker, and C. Steegborn, “Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5,” Journal of Molecular Biology, vol. 382, no. 3, pp. 790–801, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. L. A. Sazanov and J. B. Jackson, “Proton-translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria,” FEBS Letters, vol. 344, no. 2-3, pp. 109–116, 1994. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Des Rosiers, C. A. Fernandez, F. David, and H. Brunengraber, “Reversibility of the mitochondrial isocitrate dehydrogenase reaction in the perfused rat liver. Evidence from isotopomer analysis of citric acid cycle intermediates,” The Journal of Biological Chemistry, vol. 269, no. 44, pp. 27179–27182, 1994. View at Google Scholar · View at Scopus
  65. B. Comte, G. Vincent, B. Bouchard, M. Benderdour, and C. D. Rosiers, “Reverse flux through cardiac NADP+-isocitrate dehydrogenase under normoxia and ischemia,” American Journal of Physiology, vol. 283, no. 4, pp. H1505–H1514, 2002. View at Google Scholar · View at Scopus
  66. J. M. S. Lemons, H. A. Coller, X. J. Feng et al., “Quiescent fibroblasts exhibit high metabolic activity,” PLoS Biology, vol. 8, no. 10, Article ID e1000514, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. A. Pedersen, G. B. Karlsson, and J. Rydström, “Proton-translocating transhydrogenase: an update of unsolved and controversial issues,” Journal of Bioenergetics and Biomembranes, vol. 40, no. 5, pp. 463–473, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. K. Smolková, N. Bellance, F. Scandurra et al., “Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia,” Journal of Bioenergetics and Biomembranes, vol. 42, no. 1, pp. 55–67, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. I. S. Kil, S. Y. Kim, S. J. Lee, and J. W. Park, “Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-α and anticancer drugs,” Free Radical Biology and Medicine, vol. 43, no. 8, pp. 1197–1207, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. H. J. Kim, B. S. Kang, and J. W. Park, “Cellular defense against heat shock-induced oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase,” Free Radical Research, vol. 39, no. 4, pp. 441–448, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. A. H. Shin, I. S. Kil, E. S. Yang, T. L. Huh, C. H. Yang, and J. W. Park, “Regulation of high glucose-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase,” Biochemical and Biophysical Research Communications, vol. 325, no. 1, pp. 32–38, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. S. W. Shin, I. S. Kil, and J. W. Park, “Silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase by small interfering RNA enhances heat shock-induced apoptosis,” Biochemical and Biophysical Research Communications, vol. 366, no. 4, pp. 1012–1018, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. H. L. Jin, Y. K. Sung, S. K. In, and J. W. Park, “Regulation of ionizing radiation-induced apoptosis by mitochondrial NADP+-dependent isocitrate dehydrogenase,” The Journal of Biological Chemistry, vol. 282, no. 18, pp. 13385–13394, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. S. K. In, W. S. Seoung, S. Y. Hyun, S. L. Young, and J. W. Park, “Mitochondrial NADP+-dependent isocitrate dehydrogenase protects cadmium-induced apoptosis,” Molecular Pharmacology, vol. 70, no. 3, pp. 1053–1061, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. S. J. Kim, T. Y. Yune, C. T. Han et al., “Mitochondrial isocitrate dehydrogenase protects human neuroblastoma SH-SY5Y cells against oxidative stress,” Journal of Neuroscience Research, vol. 85, no. 1, pp. 139–152, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. K. H. Jung and J. W. Park, “Suppression of mitochondrial NADP+-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells,” Free Radical Research, vol. 45, no. 4, pp. 431–438, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Benderdour, G. Charron, B. Comte et al., “Decreased cardiac mitochondrial NADP+-isocitrate dehydrogenase activity and expression: a marker of oxidative stress in hypertrophy development,” American Journal of Physiology, vol. 287, no. 5, pp. H2122–H2131, 2004. View at Publisher · View at Google Scholar · View at Scopus
  78. K. Murakami, M. Haneda, T. Makino, and M. Yoshino, “Protective effect of NADP-isocitrate dehydrogenase on the paraquat-mediated oxidative inactivation of aconitase in heart mitochondria,” Environmental Toxicology and Pharmacology, vol. 22, no. 2, pp. 148–152, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. S. M. Lee, T. L. Huh, and J. W. Park, “Inactivation of NADP+-dependent isocitrate dehydrogenase by reactive oxygen species,” Biochimie, vol. 83, no. 11-12, pp. 1057–1065, 2001. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Benderdour, G. Charron, D. DeBlois, B. Comte, and C. Des Rosiers, “Cardiac mitochondrial NADP+-isocitrate dehydrogenase is inactivated through 4-hydroxynonenal adduct formation: an event that precedes hypertrophy development,” The Journal of Biological Chemistry, vol. 278, no. 46, pp. 45154–45159, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Y. Kim, J. K. Tak, and J. W. Park, “Inactivation of NADP+-dependent isocitrate dehydrogenase by singlet oxygen derived from photoactivated rose bengal,” Biochimie, vol. 86, no. 8, pp. 501–507, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. S. Young Park, S. M. Lee, S. Woo Shin, and J. W. Park, “Inactivation of mitochondrial NADP+-dependent isocitrate dehydrogenase by hypochlorous acid,” Free Radical Research, vol. 42, no. 5, pp. 467–473, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. K. Murakami and M. Yoshino, “Aluminum decreases the glutathione regeneration by the inhibition of NADP-isocitrate dehydrogenase in mitochondria,” Journal of Cellular Biochemistry, vol. 93, no. 6, pp. 1267–1271, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. E. S. Yang, C. Richter, J. S. Chun, T. L. Huh, S. S. Kang, and J. W. Park, “Inactivation of NADP+-dependent isocitrate dehydrogenase by nitric oxide,” Free Radical Biology and Medicine, vol. 33, no. 7, pp. 927–937, 2002. View at Publisher · View at Google Scholar · View at Scopus
  85. J. H. Lee, E. S. Yang, and J. W. Park, “Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite: implications for cytotoxicity and alcohol-induced liver injury,” The Journal of Biological Chemistry, vol. 278, no. 51, pp. 51360–51371, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. I. S. Kil, J. H. Lee, A. H. Shin, and J. W. Park, “Glycation-induced inactivation of NADP+-dependent isocitrate dehydrogenase: implications for diabetes and aging,” Free Radical Biology and Medicine, vol. 37, no. 11, pp. 1765–1778, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. I. S. Kil, Y. S. Lee, Y. S. Bae, T. L. Huh, and J. W. Park, “Modulation of NADP+-dependent isocitrate dehydrogenase in aging,” Redox Report, vol. 9, no. 5, pp. 271–277, 2004. View at Publisher · View at Google Scholar · View at Scopus
  88. S. A. Gupte, R. J. Levine, R. S. Gupte et al., “Glucose-6-phosphate dehydrogenase-derived NADPH fuels superoxide production in the failing heart,” Journal of Molecular and Cellular Cardiology, vol. 41, no. 2, pp. 340–349, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. C. X. Santos, L. Y. Tanaka, J. Wosniak, and F. R. Laurindo, “Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase,” Antioxidants & Redox Signaling, vol. 11, no. 10, pp. 2409–2427, 2009. View at Google Scholar · View at Scopus
  90. M. Yamaura, J. Mitsushita, S. Furuta et al., “NADPH oxidase 4 contributes to transformation phenotype of melanoma cells by regulating G2-M cell cycle progression,” Cancer Research, vol. 69, no. 6, pp. 2647–2654, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. K. Block, Y. Gorin, and H. E. Abboud, “Subcellular localization of Nox4 and regulation in diabetes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 34, pp. 14385–14390, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. P. Ježek and L. Hlavatá, “Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism,” International Journal of Biochemistry and Cell Biology, vol. 37, no. 12, pp. 2478–2503, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. P. Ježek and L. Plecitá-Hlavatá, “Mitochondrial reticulum network dynamics in relation to oxidative stress, redox regulation, and hypoxia,” International Journal of Biochemistry and Cell Biology, vol. 41, no. 10, pp. 1790–1804, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. J. C. Fernández-Checa, “Redox regulation and signaling lipids in mitochondrial apoptosis,” Biochemical and Biophysical Research Communications, vol. 304, no. 3, pp. 471–479, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. A. Dlasková, L. Hlavatá, and P. Ježek, “Oxidative stress caused by blocking of mitochondrial Complex I H+ pumping as a link in aging/disease vicious cycle,” International Journal of Biochemistry and Cell Biology, vol. 40, no. 9, pp. 1792–1805, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. L. Dang, D. W. White, S. Gross et al., “Cancer-associated IDH1 mutations produce 2-hydroxyglutarate,” Nature, vol. 462, no. 7274, pp. 739–744, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. C. M. Metallo, P. A. Gameiro, E. L. Bell et al., “Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia,” Nature, vol. 481, no. 7381, pp. 380–384, 2011. View at Publisher · View at Google Scholar
  98. C. Lu, P. S. Ward, G. S. Kapoor et al., “IDH mutation impairs histone demethylation and results in a block to cell differentiation,” Nature, vol. 483, pp. 474–478, 2012. View at Publisher · View at Google Scholar
  99. P. Koivunen, S. Lee, C. G. Duncan et al., “Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation,” Nature, vol. 483, pp. 484–488, 2012. View at Publisher · View at Google Scholar
  100. S. Turcan, D. Rohle, A. Goenka et al., “IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype,” Nature, vol. 483, pp. 479–483, 2012. View at Google Scholar
  101. B. Yang, C. Zhong, Y. Peng, Z. Lai, and J. Ding, “Molecular mechanisms of off-on switch of activities of human IDH1 by tumor-associated mutation R132H,” Cell Research, vol. 20, no. 11, pp. 1188–1200, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. T. I. Rakhmanova and T. N. Popova, “Regulation of 2-oxoglutarate metabolism in rat liver by NADP-isocitrate dehydrogenase and aspartate aminotransferase,” Biochemistry, vol. 71, no. 2, pp. 211–217, 2006. View at Publisher · View at Google Scholar · View at Scopus
  103. Y. C. Huang, N. B. Grodsky, T. K. Kim, and R. F. Colman, “Ligands of the Mn2+ bound to porcine mitochondrial NADP-dependent isocitrate dehydrogenase, as assessed by mutagenesis,” Biochemistry, vol. 43, no. 10, pp. 2821–2828, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. T. Popova, M. A. A. Pinheiro de Carvalho, L. Matasova, and L. Medvedeva, “Regulation of mitochondrial NADP-isocitrate dehydrogenase in rat heart during ischemia,” Molecular and Cellular Biochemistry, vol. 294, no. 1-2, pp. 97–105, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. M. Dange and R. F. Colman, “Each conserved active site tyr in the three subunits of human isocitrate dehydrogenase has a different function,” The Journal of Biological Chemistry, vol. 285, no. 27, pp. 20520–20525, 2010. View at Publisher · View at Google Scholar · View at Scopus