Changes in Cytochrome c Oxidase and NO in Rat Lung Mitochondria Following Iron Overload

  • Kim, Min-Sun (Division of Life Science, College of Natural Sciences, Sookmyung Women's University) ;
  • Hong, Min-A (Division of Life Science, College of Natural Sciences, Sookmyung Womens University) ;
  • Song, Eun-Sook (Division of Life Science, College of Natural Sciences, Sookmyung Womens University)
  • Published : 2009.06.30

Abstract

In this study, the effects of iron on cytochrome c oxidase (CcO) in rat lung mitochondria were examined. Similar to liver mitochondria, iron accumulated considerably in lung mitochondria (more than 2-fold). Likewise, the reactive oxygen species and nitric oxide (NO) content of mitochondria were increased by more than 50% and 100%, respectively. NO might be produced by nitric oxide synthase (NOS), eNOS and iNOS type, with particular contribution by NOS in mitochondria. The respiratory control ratio of iron overloaded lung mitochondria dropped to nearly 50% due to increased state 4. Likewise, cytochrome c oxidase activity was lowered significantly to approximately 50% due to excess iron. Real-time PCR revealed that the expression of isoforms 1 and 2 of subunit IV of CeO was enhanced greatly under excess iron conditions. Taken together, these results show that oxidative phosphorylation within lung mitochondria may be influenced by iron overload through changes in cytochrome c oxidase and NO.

Keywords

References

  1. Amold S and Kadenbach B (1997) Cell respiration is controlled by ATP, an allosteric inhibitor of cytochrome-c oxidase. Eur J Biochem 249: 350-354 https://doi.org/10.1111/j.1432-1033.1997.t01-1-00350.x
  2. Barnes PJ and Belvisi MG (1993) Nitric oxide and lung disease. Thorax 48: 1034-1043 https://doi.org/10.1136/thx.48.10.1034
  3. Brown GC (1999) Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411: 351-369 https://doi.org/10.1016/S0005-2728(99)00025-0
  4. Brown GC and 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
  5. Brunori M, Forte E, Arese M, Mastronicola D, Giuffre A, and Sarti P (2006) Nitric oxide and the respiratory enzyme. Biochim Biophys Acta 1757: 1144-1154 https://doi.org/10.1016/j.bbabio.2006.05.011
  6. Carnelli V, D'Angelo E, Pecchiari M, Ligorio M, and D'Angelo E (2003) Pulmonary dysfunction in transfusion-dependent patients with thalassemia major. Am J Respir Crit Care Med 168: 180-184 https://doi.org/10.1164/rccm.200211-1292OC
  7. Castello PR, David PS, McClure T, Crook Z, and Poyton RO (2006) Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signaling in eukaryotes. Cell Metab 3: 277-287 https://doi.org/10.1016/j.cmet.2006.02.011
  8. Castello PR, Woo DK, Ball K, Wojcik J, Liu L, and Poyton RO (2008) Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling. Proc Natl Acad Sci USA 105: 8203-8208 https://doi.org/10.1073/pnas.0709461105
  9. Chenais B, Morjani H, and 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
  10. Chomczynski P and Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156-159
  11. Claireaux AE (1975) Drugs and the lung. The effect of oxygen on the lung. J clin Path 28 Suppl. (Roy ColI Path) 9: 75-80 https://doi.org/10.1136/jcp.s3-9.1.75
  12. Cleeter MW, Cooper JM, Darley-Usmar VM, Moncada S, and Schapira AH (1994) Reversible inhibition of cytochrome c oxidase, the terminal enzyme ofthe mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 345: 50-54 https://doi.org/10.1016/0014-5793(94)00424-2
  13. 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
  14. Cooper CE and Giulivi C (2007) Nitric oxide regulation of mitochondrial oxygen consumption II: Molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 292: C1993-2003 https://doi.org/10.1152/ajpcell.00310.2006
  15. Cooper CE, Davies NA, Psychoulis M, Canevari L, Bates TE, Dobbie MS, Casley CS, and Sharpe MA (2003) Nitric oxide and peroxynitrite cause irreversible increases in the K(m) for oxygen of mitochondrial cytochrome oxidase: in vitro and in vivo studies. Biochim Biophys Acta 1607: 27-34 https://doi.org/10.1016/j.bbabio.2003.08.003
  16. 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
  17. Factor JM, Pottipati SR, Rappoport I, Rosner IK, Lesser ML, and Giardina Pl (1994) Pulmonary function abnormalities in thalassemia major and the role of iron overload. Am J Respir Crit Care Med 149: 1570-1574 https://doi.org/10.1164/ajrccm.149.6.8004315
  18. Galkin A and Brandt U (2005) Superoxide radical formation by pure complex I (NADH:Ubiquinone Oxidoreductase) from Yarrowia lipolytica. J BioI Chem 280: 30129-30135 https://doi.org/10.1074/jbc.M504709200
  19. Galleano M, Simontacchi M, and Puntarulo S (2004) Nitric oxide and iron: effect of iron overload on nitric oxide production in endotoxemia. Mol Aspects Med 25: 141-154 https://doi.org/10.1016/j.mam.2004.02.015
  20. Gutteridge JM, Quinlan GJ, and Evans TW (2001) The iron paradox of heart and lungs and its implications for acute lung injury. Free Radic Res 34: 439-443 https://doi.org/10.1080/10715760100300381
  21. Harley A, Cooper JM, and Schapira AH (1993) Iron induced oxidative stress and mitochondrial dysfunction: relevance to Parkinson's disease. Brain Res 12: 349-353 https://doi.org/10.1016/0006-8993(93)90341-J
  22. Haynes V, Elfering SL, Squires RJ, Traaseth N, Solien J, Ettl A, and Giulivi C (2003) Mitochondrial nitric-oxide synthase: role in pathophysiology. IUBMB Life 55: 599-603 https://doi.org/10.1080/15216540310001628681
  23. Horvat S, Beyer C, and Arnold S (2006) Effect of hypoxia on the transcription pattern of subunit isoforms and the kinetics of cytochrome c oxidase in cortical astrocytes and cerebellar neurons. J Neurochem 99:937-951 https://doi.org/10.1111/j.1471-4159.2006.04134.x
  24. Huttemann M, Kadenbach B, and Grossman LI (2001) Mammalian subunit IV isoforms of cytochrome c oxidase. Gene 267: 111-123 https://doi.org/10.1016/S0378-1119(01)00385-7
  25. Huttemann M, Lee I, Liu J, and Grossman LI (2007) Transcription of mammalian cytochrome c oxidase subunit IV-2 is controlled by a novel conserved oxygen responsive element. FEBS J 274: 5737-5748 https://doi.org/10.1111/j.1742-4658.2007.06093.x
  26. Kakhlon O and Cabantchik ZI (2002) The labile iron pool: characterization, measurement, and participation in cellular processes. Free Radic BioI Med 33: 1037-1046 https://doi.org/10.1016/S0891-5849(02)01006-7
  27. Kamp DW, Panduri V, Weitzman SA, and Chandel N (2002) Asbestos-induced alveolar epithelial cell apoptosis: role of mitochondrial dysfunction caused by iron-derived free radicals. Mol Cell Biochem 234-235: 153-160 https://doi.org/10.1023/A:1015949118495
  28. Kolb JP, Paul-Eugene N, Damais C, Yamaoka K, Drapier JC, and 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
  29. Lacza Z, Puskar M, Figueroa JP, Zhang J, Rajapakse N, and Busija DW (2001) Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia. Free Rad Biol Med 31: 1609-1615 https://doi.org/10.1016/S0891-5849(01)00754-7
  30. Lancaster Jr JR and Hibbs Jr JB (1990) EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages. Proc Natl Acad Sci USA 87: 1223-1227 https://doi.org/10.1073/pnas.87.3.1223
  31. Levi S, Luzzago A, Cesareni G, Cozzi A, Franceschinelli F, Albertini A, and 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
  32. Li Y, Park JS, Deng JR, and Bai Y (2006) Cytochrome c oxidase subunit IV is essential for assembly and respiratory function of the enzyme complex. J Bioenerg Biomembr 38: 283-291 https://doi.org/10.1007/s10863-006-9052-z
  33. Liu X, Cheng C, Zorko N, Cronin S, Chen YR, and Zweier JL (2004) Biphasic modulation of vascular nitric oxide catabolism by oxygen. Am J Physiol Heart Circ Physiol 287: H2421-2426 https://doi.org/10.1152/ajpheart.00487.2004
  34. Napier I, Ponka P, and 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
  35. Negre-Salvayre A, Hirtz C, Carrera G, Cazenave R, Troly M, Salvayre R, Penicaud L, and Casteilla L (1997) A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. FASEB J 11: 809-815
  36. Nestel FP, Greene RN, Kichian K, Ponka P, and Lapp WS (2000) Activation of macrophage cytostatic effector mechanisms during acute graft-versus-host disease: release of intracellular iron and nitric oxide-mediated cytostasis. Blood 96: 1836-1843
  37. O'Connell MJ, Snape SD, and Nunn IF (1991) An early marker of hyperoxic lung injury in the rat and its pharmacological modulation. Br J Anaesth 66: 697-702 https://doi.org/10.1093/bja/66.6.697
  38. Pande SV and Blanchaer MC (1971) Reversible inhibition of mitochondria adenosine diphosphate phosphorylation by long chain acyl coenzyme A esters. J Biol Chem 25: 402-411
  39. Pearce LL, Kanai AJ, Birder LA, Pitt BR, and Peterson J (2002) The catabolic fate of nitric oxide: the nitric oxide oxidase and peroxynitrite reductase activities of cytochrome oxidase. J BioI Chem 277: 13556-13562 https://doi.org/10.1074/jbc.M109838200
  40. Persichini T, Mazzone V, Polticelli F, Moreno S, Venturini G, Clementi E, and Colasanti M (2005) Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neurosci Lett 384: 254-259 https://doi.org/10.1016/j.neulet.2005.04.085
  41. Ramachandran A, Ceaser E, and Darley-Usmar VM (2004) Chronic exposure to nitric oxide alters the free iron pool in endothelial cells: role of mitochondrial respiratory complexes and heat shock proteins. Proc Natl Acad Sci USA 101: 384-389 https://doi.org/10.1073/pnas.0304653101
  42. Sharpe MA and Cooper CE (1998) Interaction of peroxynitrite with mitochondrial cytochrome oxidase. Catalytic production ofnitric oxide and irreversible inhibition of enzyme activity.J BioI Chem 273: 30961-30972 https://doi.org/10.1074/jbc.273.47.30961
  43. Thannickal VJ and Fanburg BL (2000) Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279: L1005-1028
  44. Trueblood CE and Poyton RO (1987) Differential regulation of the two genes encoding Saccharomycescerevisiaecytochrome c oxidase subunit V by heme and the HAP2 and REO1 genes. Mol Cell BioI 7:3520-3526
  45. Turrens JF, Alexandre A, and Lehninger AL (1985) Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch Biochem Biophys 237: 408-414 https://doi.org/10.1016/0003-9861(85)90293-0
  46. Valkonen M and Kuusi T (1997) Spectrophotometric assay for total peroxyl radical-trapping antioxidant potential in human serum. J Lipid Res 38: 823-833
  47. Vijayasarathy C, Biunno I, Lenka N, Yang M, Basu A, Hall IP, and Avadhani NG (1998) Variations in the subunit content and catalytic activity of the cytochrome c oxidase complex from different tissues and different cardiac compartments. Biochim Biophys Acta 371: 71-82 https://doi.org/10.1016/S0005-2736(97)00278-2
  48. Waterland RA, Basu A, Chance B, and Poyton RO (1991) The isoforms of yeast cytochrome c oxidase subunit V alter the in vivo kinetic properties of the holoenzyme. J Biol Chem 266: 4180-4186