Animal cells and systems

The Korean Society for Integrative Biology (한국통합생물학회)
권호 표지
DOI QR코드

DOI QR Code

Temporal changes in mitochondrial activities of rat heart after a single injection of iron, including increased complex II activity

  • Kim, Mi-Sun (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Song, Eun-Sook (Division of Life Science, College of Natural Sciences, Sookmyung Women's University)
  • Received : 2009.12.26
  • Published : 2010.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Male rats were given a single injection of iron, and temporal changes in iron content and iron-induced effects were examined in heart cellular fractions. Over a period of 72 h, the contents of total and labile iron, reactive oxygen species, and NO in tissue homogenate, nuclear debris, and postmitochondrial fractions were mostly constant, but in mitochondria they continuously increased. An abrupt decrease in membrane potential and NAD(P)H at 12 h was also found in mitochondria. The respiratory control ratio was reduced slowly with a slight recovery at 72 h, suggesting uncoupling by iron.While the ATP content of tissue homogenate decreased steadily until 72 h, it showed a prominent increase in mitochondria at 12 h. Total iron and calcium concentration also progressively increased in mitochondria over 72 h. Enzyme activity of the oxidative phosphorylation system was significantly altered by iron injection: activities of complexes I, III, and IV were reduced considerably, but complex II activity and the ATPase activity of complex V were enhanced. A reversal of activity in complexes I and II at 12 h suggested reverse electron transfer due to iron overload. These results support the argument that mitochondrial activities including oxidative phosphorylation are modulated by excessive iron.

Keywords

References

  1. Atamna H. 2004. Heme, iron, and the mitochondrial decay of ageing. Ageing Res Rev. 3:303-318. https://doi.org/10.1016/j.arr.2004.02.002
  2. Atamna H, Walter PB, Ames BN. 2002. The role of heme and iron-sulfur dusters in mitochondrial biogenesis, maintenance, and decay with age. Arch Biochem Biophys. 397:345-353.
  3. Balaban RS. 2009. Domestication of the cardiac mitochondrion for energy conversion. J Mol Cell Cardiol. 46:832-841. https://doi.org/10.1016/j.yjmcc.2009.02.018
  4. Barrientos A. 2002. In vivo and in organello assessment of oxphos activities. Methods. 26:307-316. https://doi.org/10.1016/S1046-2023(02)00036-1
  5. Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakay JL, Parker N. 2004. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Rad Biol Med. 37:755-767. https://doi.org/10.1016/j.freeradbiomed.2004.05.034
  6. Brewer GJ. 2007. Iron and copper toxicity in diseases of aging particularly Atherosclerosis and Alzheimer's Disease. Exp Biol Med. 232:323-335.
  7. Britton RS, Leicester KL, Bacon BR. 2002. Iron toxicity and chelation therapy. lnt J Hematol. 76:219-228. https://doi.org/10.1007/BF02982791
  8. Brown GC, Cooper CE. 1994. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett. 356:295-298. https://doi.org/10.1016/0014-5793(94)01290-3
  9. Castelle C, Guiral M, Malarte G, Ledgham F, Leroy G, Brugna M, Giudici-Orticoni M. 2008. A new $iron-oxidizing/O_{2}-reducing$ supercomplex spanning both inner and outer membranes, isolated from the extreme acidophile Acidithiobacillus ferrooxidans. J Biol Chem. 283:25803-25811. https://doi.org/10.1074/jbc.M802496200
  10. Chance B, Hollunger G. 1961. The interaction of energy and electron transfer reactions in mitochondria I. General properties and nature of the products of succinate-linked reduction of pyridine nucleotide. J Biol Chem. 236:1534-1543.
  11. Chenais B, Morjani H, Drapier JC. 2002. Impact of endogenous nitric oxide on microglial cell energy metabolism and labile iron pool. J Neurochem. 81:615-623. https://doi.org/10.1046/j.1471-4159.2002.00864.x
  12. Cooper CE. 2002. Nitric oxide and cytochrome oxidase: substrate, inhibitor or effector? Trends Biochem Sci. 27:33-39. https://doi.org/10.1016/S0968-0004(01)02035-7
  13. Csordas G, Hajnoczky G. 2009. SR/ER-mitochondrial local communication: calcium and ROS. Biochim Biophys Acta. 1787:1352-1362. https://doi.org/10.1016/j.bbabio.2009.06.004
  14. Das AM, Harris DA. 1990. Intracellular calcium as a regulator of the mitochondrial A TP synthase in cultured cardiomyocytes. Biochem Soc Trans. 18:554-555. https://doi.org/10.1042/bst0180554
  15. Eastabrook RW 1967. Mitochondrial respiratory control and the polarographic measurement of ADP:O ratio. Methods Enzymol. 10:41-47. https://doi.org/10.1016/0076-6879(67)10010-4
  16. Emaus RD, Grunwald R, LeMasters JJ. 1986. Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties. Biochim Biophys Acta. 950:436-448.
  17. Feissner RF, Skalska J, Gaum WE, Sheu SS. 2009. Crosstalk signaling between mitochondrial $Ca^{2+}$ and ROS. Front Biosci. 14:1197-1218.
  18. Giuffre A, Sarti P, D'Itri E, Buse G, Soulimane T, Brunori M. 1996. On the mechanism of inhibition of cytochrome c oxidase by nitric oxide. J Biol Chem. 271(52):33404-33408. https://doi.org/10.1074/jbc.271.52.33404
  19. Gogvadze V, Walter PB, Ames BN. 2002. Fe(2+) induces a transient Ca(2+) release from rat liver mitochondria. Arch Biochem Biophys. 398:198-202. https://doi.org/10.1006/abbi.2001.2721
  20. Gorman AC, Thomas MY. 1978. Changes in the intracellular concentaration of free calcium ions in a pace-marker neurine, measured with the metallochronic indicator dye arsenazo III. J Physiol. 275:357-376. https://doi.org/10.1113/jphysiol.1978.sp012194
  21. Graier WF, Frieden M, Malli R. 2007. Mitochondria and Ca(2+) signaling: old guests, new functions. Pflugers Arch. 455:375-396. https://doi.org/10.1007/s00424-007-0296-1
  22. Grivennikova VG, Kotlyar AB, Karliner JS, Cecchini G, Vinogradov AD. 2007. Redox-dependent change of nucleotide affinity to the active site of the mammalian complex I. Biochemistry. 46:10971-10978. https://doi.org/10.1021/bi7009822
  23. Hansford RG, Zorov D. 1998. Role of mitochondrial calcium transport in the control of substrate oxidation. Mol Cell Biochem. 184:359-369. https://doi.org/10.1023/A:1006893903113
  24. Harley A, Cooper JM, Schapira AH. 1993. Iron induced oxidative stress and mitochondrial dysfunction: relevance to Parkinson's disease. Brain Res. 12:349-353.
  25. Hulsmann WC, Bethlem J, Meijer AE, Fleury P, Schellens JP. 1967. Myopathy with abnormal structure and function of muscle mitochondria. J Neurol Neurosurg Psychiatry. 30:519-525. https://doi.org/10.1136/jnnp.30.6.519
  26. Kanai AJ, Pearce LL, Clemens PR, Birder LA, VanBibber MM, Choi SY, de Groat WC, Peterson J. 2001. Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA. 98:14126-14131. https://doi.org/10.1073/pnas.241380298
  27. Kim M, Hong M, Song E. 2009. Changes in cytochrome c oxidase and NO in rat lung mitochondria following iron overload. Animal Cells Systems. 13:105-112. https://doi.org/10.1080/19768354.2009.9647200
  28. Kim M, Kim J, Cheon C-I, Cho DH, Park JH, Kim KI, Lee KY, Song E. 2008. Increased expression of the $F_{l}Fo$ ATP synthase in response to iron in heart mitochondria. BMB Reports. 41:153-157. https://doi.org/10.5483/BMBRep.2008.41.2.153
  29. Kolb JP, Paul-Eugene N, Damais C, Yamaoka K, Drapier JC, Dugas B. 1994. Interleukin-4 stimulates cGMP production by IFN-gamma-activated human monocytes. Involvement of the nitric oxide synthase pathway. J Biol Chem. 269:9811-9816.
  30. Lehninger AL. 1970. Mitochondria and calcium ion transport. Biochem J. 119:129-138. https://doi.org/10.1042/bj1190129
  31. Lesnefsky EJ. 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
  32. Levi S, Luzzago A, Cesareni G, Cozzi A, Franceschinelli F, Albertini A, Arosio P. 1988. Mechanism of ferritin iron uptake: activity of the H-chain and deletion mapping of the ferro-oxidase site. A study of iron uptake and ferro-oxidase activity of human liver, recombinant H-chain ferritins, and of two H-chain deletion mutants. J Biol Chem. 263:18086-18092.
  33. Levi S, Rovida E. 2009. The role of iron in mitochondrial function. Biochim Biophys Acta. 1790:629-636. https://doi.org/10.1016/j.bbagen.2008.09.008
  34. Lill R, Dutkiewicz R, Elsasser HP, Hausmann A, Netz DJ, Pierik AJ, Stehling O, Urzica E, Muhlenhoff U. 2006. Mechanisms of iron-sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes. Biochim Biophys Acta. 1763:652-667. https://doi.org/10.1016/j.bbamcr.2006.05.011
  35. Link G, Saada A, Pinson A, Konijn AM, Hershko C. 1998. Mitochondrial respiratory enzymes are a major target of iron toxicity in rat heart cells. J Lab Clin Med. 131:466-474. https://doi.org/10.1016/S0022-2143(98)90148-2
  36. Liu T, O'Rourke B. 2009. Regulation of mitochondrial $Ca^{2+}$ and its effects on energetics and redox balance in normal and failing heart. J Bioenerg Biomembr. 41:127-132. https://doi.org/10.1007/s10863-009-9216-8
  37. Lundin A, 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
  38. Machida K, Tanaka T. 1999. Farnesol-induced generation of reactive oxygen species dependent on mitochondrial transmembrane potential hyperpolarization mediated by F(0)F(1)-ATPase in yeast. FEBS Lett. 462:108-112. https://doi.org/10.1016/S0014-5793(99)01506-9
  39. Mao P, Ardeshiri A, Jacks R, Yang S, Hum PD, Alkayed NJ. 2007. Mitochondrial mechanism of neuroprotection by CART. Eur J Neurosc. 26:624-632. https://doi.org/10.1111/j.1460-9568.2007.05691.x
  40. Masini A, Trenti T, Ceccarelli D, Muscatello U. 1987. The effect of a ferric iron complex on isolated rat liver mitochondria. III. Mechanistic aspects of iron induced calcium efflux. Biochim Biophys Acta. 891:150-156. https://doi.org/10.1016/0005-2728(87)90007-7
  41. Munoz M, Villar I, Garcia-Erce JA. 2009. An update on iron physiology. World J Gastroenterol. 15:4617-4626. https://doi.org/10.3748/wjg.15.4617
  42. Napier I, Ponka P, Richardson DR. 2005. Iron trafficking in the mitochondrion: novel pathways revealed by disease. Blood. 105:1867-1874. https://doi.org/10.1182/blood-2004-10-3856
  43. Pande SV, Blanchaer MC. 1971. Reversible inhibition of mitochondrial adenosine diphosphate phosphorylation by long chain acyl coenzyme A esters. J Biol Chem. 246:402-411.
  44. Pearce LL, Martinez-Bosch S, Manzano EL, Winnica DE, Epperly MW, Peterson J. 2009. The resistance of electron-transport chain Fe-S clusters to oxidative damage during the reaction of peroxynitrite with mitochondrial complex II and rat-heart pericardium. Nitric Oxide. 20:135-142. https://doi.org/10.1016/j.niox.2008.12.001
  45. Richardson DR, Lok HC. 2008. The nitric oxide-iron interplay in mammalian cells: transport and storage of dinitrosyl iron complexes. Biochim Biophys Acta. 1780:638-651. https://doi.org/10.1016/j.bbagen.2007.12.009
  46. 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
  47. Romslo I, Flatmark T. 1973. Energy-dependent accumulation of iron by isolated rat liver mitochondria. II. Relationship to the active transport of $Ca^{2+}$, Biochim Biophys Acta. 325:38-46. https://doi.org/10.1016/0005-2728(73)90148-5
  48. Rouault TA, Tong WH. 2005. Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol. 6:345-351.
  49. Territo PR, Mootha VK, French SA, Balaban RS. 2000. Ca(2+) activation of heart mitochondrial oxidative phosphorylation: role of the F(0)/F(1)-ATPase. Am J Physiol Cell Physiol. 278:C423-435. https://doi.org/10.1152/ajpcell.2000.278.2.C423
  50. Valkonen M, Kuusi T. 1997. Spectrophotometric assay for total peroxyl radical-trapping antioxidant potential in human serum. J Lipid Res. 38:823-833.
  51. Vatassery GT. 2004. Impairment of brain mitochondrial oxidative phosphorylation accompanying vitamin E oxidation induced by iron or reactive nitrogen species: a selective review. Neurochem Res. 29:1951-1959. https://doi.org/10.1007/s11064-004-6870-4
  52. Vinogradov AD, Grivennikova VG. 2005. Generation of superoxide-radical by the NADH:Ubuquinone oxidore-ductase of heart mitochondria. Biochemistry (Moscow) 70:120-127. https://doi.org/10.1007/s10541-005-0090-7
  53. Walter PB, Knutson MD, Paler-Martinez A, Lee S, Xu Y, Viteri FE, Ames BN. 2002. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci USA. 99:2264-2269. https://doi.org/10.1073/pnas.261708798
  54. Watts RN, Hawkins C, Ponka P, Richardson DR. 2006. Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein. Proc Natl Acad Sci USA. 103:7670-7675. https://doi.org/10.1073/pnas.0602515103
  55. Ying W. 2008. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal. 10:179-206. https://doi.org/10.1089/ars.2007.1672