BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Increased expression of the F1Fo ATP synthase in response to iron in heart mitochondria

  • Kim, Mi-Sun (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Kim, Jin-Sun (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Cheon, Choong-Ill (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Cho, Dae-Ho (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Park, Jong-Hoon (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Kim, Keun-Il (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Lee, Kyo-Young (Department of Pathology, Saint Mary's Hospital) ;
  • Song, Eun-Sook (Division of Life Science, College of Natural Sciences, Sookmyung Women's University)
  • Received : 2007.09.07
  • Accepted : 2007.12.17
  • Published : 2008.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

The objective of the present study was to identify mitochondrial components associated with the damage caused by iron to the rat heart. Decreased cell viability was assessed by increased presence of lactate dehydrogenase (LDH) in serum. To assess the functional integrity of mitochondria, Reactive Oxygen Species (ROS), the Respiratory Control Ratio (RCR), ATP and chelatable iron content were measured in the heart. Chelatable iron increased 15-fold in the mitochondria and ROS increased by 59%. Deterioration of mitochondrial function in the presence of iron was demonstrated by low RCR (46% decrease) and low ATP content (96% decrease). Using two dimensional gel electrophoresis (2DE), we identified alterations in 21 mitochondrial proteins triggered by iron overload. Significantly, expression of the $\alpha$, $\beta$, and d subunits of $F_1F_o$ ATP synthase increased along with the loss of ATP. This suggests that the $F_1F_o$ ATP synthase participates in iron metabolism.

Keywords

References

  1. Atamna, H., Walter, P. B. and Ames, B. N. (2002) The Role of Heme and Iron-Sulfur Clusters in Mitochondrial Biogenesis, Maintenance, and Decay with Age. Arch. Biochem. Biophys. 397, 345-353 https://doi.org/10.1006/abbi.2001.2671
  2. Parkes, J. G., Hussain, R. A., Olivieri, N. F. and Templeton, D. M. (1993) Effects of iron loading on uptake, speciation, and chelation of iron in cultured myocardial cells. J. Lab. Clin. Med. 122, 36-47
  3. Byler, R. M., Sherman, N. A., Wallner, J. S. and Horwitz, L. D. (1994) Hydrogen peroxide cytotoxicity in cultured cardiac myocytes is iron dependent. Am. J. Physiol. 266, 121-127 https://doi.org/10.1152/ajpcell.1994.266.1.C121
  4. Turoczi, T., Jun, L., Cordis, G., Morris, J. E., Maulik, N., Stevens, R. G. and Das, D. K. (2003) HFE mutation and dietary iron content interact to increase ischemia/reperfusion injury of the heart in mice. Circ. Res. 92, 1240-1246 https://doi.org/10.1161/01.RES.0000076890.59807.23
  5. Bacon, B. R., Britton, R. S. and O'Neill, R. (1989) Effects of vitamin E deficiency on hepatic mitochondrial lipid peroxidation and oxidative metabolism in rats with chronic dietary iron overload. Hepatology. 9, 398-404 https://doi.org/10.1002/hep.1840090309
  6. Vatassery, G. T. (2004) Impairment of brain mitochondrial oxidative phosphorylation accompanying vitamin E oxidation induced by iron or reactive nitrogen species: a selective review. Neurochem. Res. 11, 1951-1959
  7. Vatassery, G. T., DeMaster, E. G., Lai, J. C., Smith, W. E. and Quach, H. T. (2004) Iron uncouples oxidative phosphorylation in brain mitochondria isolated from vitamin E-deficient rats. Biochim. Biophys. Acta 1688, 265-273 https://doi.org/10.1016/j.bbadis.2003.12.013
  8. Pucheu, S., Coudray, C., Tresallet, N., Favier, A. and de Leiris, A. J. (1993) Effect of iron overload in the isolated ischemic and reperfused rat heart. Cardiovasc. Drugs Ther. 701-711
  9. Link, G., Saada, A., Pinson, A., Konijn, A. M. and Hershko, C. (1998) Mitochondrial respiratory enzymes are a major target of iron toxicity in rat heart cells. J. Lab. Clin. Med. 131, 466-473 https://doi.org/10.1016/S0022-2143(98)90148-2
  10. Kim, N., Lee, Y., Kim, H., Joo, H., Youm, J. B., Park, W. S., Warda, M., Cuong, D. V. and Han, J. (2006) Potential biomarkers for ischemic heart damage identified in mitochondrial proteins by comparative proteomics. Proteomics 6, 1237-1249 https://doi.org/10.1002/pmic.200500291
  11. Belogrudov, G. I. (1996) Mitochondrial ATP Synthase: Fe2+-Catalyzed Fragmentation of the Soluble F1-ATPase. Arch. Biochem. Biophys. 335, 131-138 https://doi.org/10.1006/abbi.1996.0490
  12. Lesnefsky, E. J. (1994) Tissue iron overload and mechanisms of iron-catalyzed oxidative injury. Adv. Exp. Med. Biol. 366, 129-146 https://doi.org/10.1007/978-1-4615-1833-4_10
  13. Comelli, M., Di Pancrazio, F. and Mavelli, I. (2003) Apoptosis is induced by decline of mitochondrial ATP synthesis in erythroleukemia cells. Free Radic. Biol. Med. 34, 1190-1199 https://doi.org/10.1016/S0891-5849(03)00107-2
  14. Hua, S., Inesi, G., Nomura, H. and Toyoshima, C. (2002) Fe(2+)-catalyzed oxidation and cleavage of sarcoplasmic reticulum ATPase reveals Mg(2+) and Mg(2+)-ATP sites. Biochemistry 41, 11405-11410 https://doi.org/10.1021/bi026181u
  15. Florea, L., Di Francesco, V., Miller, J., Turner, R., Yao, A., Harris, M., Walenz, B., Mobarry, C., Merkulov, G.. V., Charlab, R., Dew, I., Deng, Z., Istrail, S., Li, P. and Sutton, G. (2005) Gene and alternative splicing annotation with AIR. Genome Res. 15, 54-66 https://doi.org/10.1101/gr.2889405
  16. Hojlund, K., Wrzesinski, K., Larsen, P. M., Fey, S. J., Roepstorff, P., Handberg, A., Dela, F., Vinten, J., McCormack, J. G., Reynet, C. and Beck-Nielsen, H. (2003) Proteome Analysis Reveals Phosphorylation of ATP Synthase beta-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes. J. Biol. Chem. 278, 10436-10442 https://doi.org/10.1074/jbc.M212881200
  17. He, Z. G., Hu, Y. H., Zhong, H., Hu, W. X. and Xu, J. (2005) Preliminary proteomic analysis of Thiobacillus ferrooxidans growing on elemental sulphur and Fe2+ separately. J. Biochem. Mol. Biol. 38, 307-313 https://doi.org/10.5483/BMBRep.2005.38.3.307
  18. Romslo, I. (1975) Energy-dependent accumulation of iron by isolated rat liver mitochondria. IV. Relationship to the energy state of the mitochondria. Biochim. Biophys. Acta 387, 69-79 https://doi.org/10.1016/0005-2728(75)90052-3
  19. Nijtmans, L.G., Henderson, N. S., Attardi, G. and Holt, I. J. (2001) Impaired ATP synthase assembly associated with a mutation in the human ATP synthase subunit 6 gene. J. Biol. Chem. 276, 6755-6762 https://doi.org/10.1074/jbc.M008114200
  20. Kadenbach, B. (2003) Intrinsic and extrinsic uncoupling of oxidative phosphorylation. Biochim. Biophys. Acta 1604, 77-94 https://doi.org/10.1016/S0005-2728(03)00027-6
  21. Brookes, P. S. (2005) Mitochondrial H(+) leak and ROS generation: an odd couple. Free Radic. Biol. Med. 38, 12-23 https://doi.org/10.1016/j.freeradbiomed.2004.10.016
  22. Sullivan, P. G., Springer, J. E., Hall, E. D. and Scheff, S. W. (2004) Mitochondrial uncoupling as a therapeutic target following neuronal injury. J. Bioenerg. Biomembr. 36, 353-356 https://doi.org/10.1023/B:JOBB.0000041767.30992.19
  23. Guo, J. X., Jacobson, S. l. and Brown, D. L. (1986) Rearrangement of tubulin, actin and myosin in cultured ventricular cardiomyocytes of the adult rat. Cell. Motil. Cytoskel. 6, 291-304 https://doi.org/10.1002/cm.970060306
  24. Lundin, A. and Thore, A. (1975) Analytical information obtainable by evaluation of the time course of firefly bioluminescence in the assay of ATP. Anal. Biochem. 66, 47-63 https://doi.org/10.1016/0003-2697(75)90723-X
  25. Valkonen, M. and Kuusi, T. (1997) Spectrophotometric assay for total peroxyl radical-trapping antioxidant potential in human serum. J. Lipid Res. 38, 823-833
  26. Eastabrook, R. W. (1967) Mitochondrial respiratory control and the polarographic measurement of ADP:O ratio. Meth. Enzymol. 10, 41-47 https://doi.org/10.1016/0076-6879(67)10010-4
  27. Bauer, J. D. (1982) Chemical Laboratory Methods C. V. Mosby Co, St. Louis
  28. Epsztejn, S., Kakhlon, O., Glickstein, H., Breuer, W. and Cabantchik, Z. I. (1997) Fluorescence analysis of the labile iron pool of mammalian cells. Anal. Biochem. 248, 31-40 https://doi.org/10.1006/abio.1997.2126
  29. Li, M., Xiao, Z. Q., Chen, Z. C., Li, J. L., Li, C., Zhang, P. F. and Li, M. Y. (2007) Proteomic analysis of the aging-related proteins in human normal colon epithelial tissue. BMB reports (formerly J. Biochem. Mol. Biol.) 40, 72-81 https://doi.org/10.5483/BMBRep.2007.40.1.072
  30. Klose, J. and Kobalz, U. (1995) Two-dimensional electrophoresis of proteins: an updated protocol and implications for a functional analysis of the genome. Electrophoresis. 16, 1034-1059 https://doi.org/10.1002/elps.11501601175

Cited by

  1. Construction of eukaryotic expression vector encoding ATP synthase lipid-binding protein-like protein gene of Sj and its expression in HeLa cells vol.23, pp.2, 2008, https://doi.org/10.1016/S1000-1948(08)60029-5
  2. Proteomic analysis of silver nanoparticle toxicity in rat vol.2, pp.4, 2010, https://doi.org/10.1007/BF03217491
  3. Phosphorylation ofβsubunit in F1F0ATP synthase is associated with increased iron uptake in iron-overloaded heart mitochondria vol.17, pp.6, 2013, https://doi.org/10.1080/19768354.2013.867901
  4. Transition metals and mitochondrial metabolism in the heart vol.55, 2013, https://doi.org/10.1016/j.yjmcc.2012.05.014
  5. Iron transport by proteoliposomes containing mitochondrial F1Fo ATP synthase isolated from rat heart vol.92, pp.4, 2010, https://doi.org/10.1016/j.biochi.2010.01.014
  6. Ethanol Dose- and Time-dependently Increases α and β Subunits of Mitochondrial ATP Synthase of Cultured Neonatal Rat Cardiomyocytes vol.82, pp.5, 2015, https://doi.org/10.1272/jnms.82.237
  7. Silencing of FAD synthase gene in Caenorhabditis elegans upsets protein homeostasis and impacts on complex behavioral patterns vol.1820, pp.4, 2012, https://doi.org/10.1016/j.bbagen.2012.01.012
  8. Mild intracellular acidification by dexamethasone attenuates mitochondrial dysfunction in a human inflammatory proximal tubule epithelial cell model vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-10483-y
  9. Effects of ATP and ADP on iron uptake in rat heart mitochondria vol.14, pp.4, 2010, https://doi.org/10.1080/19768354.2010.525836
  10. Temporal changes in mitochondrial activities of rat heart after a single injection of iron, including increased complex II activity vol.14, pp.2, 2010, https://doi.org/10.1080/19768354.2010.486936
  11. Iron Depletion Affects Genes Encoding Mitochondrial Electron Transport Chain and Genes of Non­Oxidative Metabolism, Pyruvate Kinase and Lactate Dehydrogenase, in Primary Human Cardiac Myocytes Cultured upon Mechanical Stretch vol.7, pp.10, 2018, https://doi.org/10.3390/cells7100175