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Mitochondrion: A Missing Link in Asthma Pathogenesis

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Mitochondrial Function in Lung Health and Disease

Part of the book series: Respiratory Medicine ((RM,volume 15))

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Abstract

Asthma is a multifactorial airway disease with airway hyperresponsiveness, airway inflammation, goblet cell metaplasia, and structural changes including airway smooth muscle proliferation and subepithelial fibrosis. Airway epithelial injury and apoptosis is an important triggering and amplification point in asthma pathogenesis, and mitochondrial dysfunction in epithelial cells appears to play an important role. On the other hand, mitochondrial biogenesis is an important aspect of smooth muscle hypertrophy and fibroblast proliferation, which leads to airway remodeling and hyperresponsiveness. In mice, preexisting mitochondrial dysfunction has been shown to potentiate allergic experimental asthma. In this review, we summarize the current understanding on the involvement of mitochondria in asthma pathogenesis, discuss the probable points of intersection between lung pathobiology and mitochondrial biology, and speculate regarding the road ahead. Mitochondrial influence on cellular oxidative and nitrative stress, apoptosis, and calcium homeostasis is covered in detail, as well as the role of molecules like nitric oxide synthase, asymmetric dimethyl arginine (ADMA), and peroxynitrite on mitochondrial function, epithelial injury, and asthma. Potential therapeutic strategies involving coenzyme Q, vitamin E, and esculetin that influence mitochondrial function and alleviate features of asthma are also discussed.

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References

  1. Ernster L, Schatz G. Mitochondria: a historical review. J Cell Biol. 1981;91:227–55.

    CAS  PubMed Central  Google Scholar 

  2. Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148:1145–59.

    CAS  PubMed  Google Scholar 

  3. Chacinska A, Koehler CM, Milenkovic D, Lithgow T, Pfanner N. Importing mitochondrial proteins: machineries and mechanisms. Cell. 2009;138:628–44.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87:99–163.

    CAS  PubMed  Google Scholar 

  5. Crow MT, Mani K, Nam YJ, Kitsis RN. The mitochondrial death pathway and cardiac myocyte apoptosis. Circ Res. 2004;95:957–70.

    CAS  PubMed  Google Scholar 

  6. Tal MC, Iwasaki A. Mitoxosome: a mitochondrial platform for cross-talk between cellular stress and antiviral signaling. Immunol Rev. 2011;243:215–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Masoli M, Fabian D, Holt S, Beasley R. Global Initiative for Asthma (GINA) program: the global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004;59:469–78.

    PubMed  Google Scholar 

  8. Braman SS. The global burden of asthma. Chest. 2006;130:4S–12.

    PubMed  Google Scholar 

  9. King CS, Moores LK. Clinical asthma syndromes and important asthma mimics. Respir Care. 2008;53:568–80.

    PubMed  Google Scholar 

  10. The Global Asthma Report 2011. Paris: The International Union Against Tuberculosis and Lung Disease; 2011.

    Google Scholar 

  11. Agrawal A, Mabalirajan U, Ahmad T, Ghosh B. Emerging interface between metabolic syndrome and asthma. Am J Respir Cell Mol Biol. 2011;44:270–5. Review.

    CAS  PubMed  Google Scholar 

  12. Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc. 2009;6:256–9.

    CAS  PubMed  Google Scholar 

  13. Monteseirín J. Neutrophils and asthma. J Investig Allergol Clin Immunol. 2009;19:340–54.

    PubMed  Google Scholar 

  14. Wang W, Li JJ, Foster PS, Hansbro PM, Yang M. Potential therapeutic targets for steroid-resistant asthma. Curr Drug Targets. 2010;11:957–70.

    CAS  PubMed  Google Scholar 

  15. Tattersfield AE. The site of the defect in asthma. Neurohumoral, mediator or smooth muscle? Chest. 1987;91:184S–9.

    CAS  PubMed  Google Scholar 

  16. Hirst SJ, Lee TH. Airway smooth muscle as a target of glucocorticoid action in the treatment of asthma. Am J Respir Crit Care Med. 1998;158:S201–6.

    CAS  PubMed  Google Scholar 

  17. Konradova V, Copova C, Sukova B, Houstek J. Ultrastructure of the bronchial epithelium in three children with asthma. Pediatr Pulmonol. 1985;1:182–7.

    CAS  PubMed  Google Scholar 

  18. Hayashi T, Ishii A, Nakai S, Hasegawa K. Ultrastructure of goblet-cell metaplasia from Clara cell in the allergic asthmatic airway inflammation in a mouse model of asthma in vivo. Virchows Arch. 2004;444:66–73.

    PubMed  Google Scholar 

  19. Mabalirajan U, Dinda AK, Kumar S, Roshan R, Gupta P, Sharma SK, Ghosh B. Mitochondrial structural changes and dysfunction are associated with experimental allergic asthma. J Immunol. 2008;181:3540–8.

    CAS  PubMed  Google Scholar 

  20. Aguilera-Aguirre L, Bacsi A, Saavedra-Molina A, Kurosky A, Sur S, Boldogh I. Mitochondrial dysfunction increases allergic airway inflammation. J Immunol. 2009;183:5379–87.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Gvozdjáková A, Kucharská J, Bartkovjaková M, Gazdíková K, Gazdík FE. Coenzyme Q10 supplementation reduces corticosteroids dosage in patients with bronchial asthma. Biofactors. 2005;25:235–40.

    PubMed  Google Scholar 

  22. Fogarty A, Lewis S, Weiss S, Britton J. Dietary vitamin E, IgE concentration, and atopy. Lancet. 2000;356:1573–4.

    CAS  PubMed  Google Scholar 

  23. Blesa S, Cortijo J, Mata M, Serrano A, Closa D, Santangelo F, et al. Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen. Eur Respir J. 2003;21:394–400.

    CAS  PubMed  Google Scholar 

  24. Gredilla R. DNA damage and base excision repair in mitochondria and their role in aging. J Aging Res. 2010;2011:257093.

    PubMed Central  PubMed  Google Scholar 

  25. Taylor RW, Turnbull DM. Mitochondrial DNA mutations in human disease. Nat Rev Genet. 2005;6:389–402.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Ghosh B, Batra J, Sharma S, Kumar A, Sharma M, Chatterjee R, Mabalirajan U. Genetic components of asthma: current status and future goals. Int Rev Asthma (Jpn). 2006;8:67–88.

    Google Scholar 

  27. Kumar A, Ghosh B. Genetics of asthma: a molecular biologist perspective. Clin Mol Allergy. 2009;7:7.

    PubMed Central  PubMed  Google Scholar 

  28. Ober C, Hoffjan S. Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun. 2006;7:95–100.

    CAS  PubMed  Google Scholar 

  29. Oliveti JF, Kercsmar CM, Redline S. Pre- and perinatal risk factors for asthma in inner city African-American children. Am J Epidemiol. 1996;143:570–7.

    CAS  PubMed  Google Scholar 

  30. Litonjua AA, Carey VJ, Burge HA, Weiss ST, Gold DR. Parental history and the risk for childhood asthma. Does mother confer more risk than father? Am J Respir Crit Care Med. 1998;158:176–81.

    CAS  PubMed  Google Scholar 

  31. Soto-Quiros ME, Silverman EK, Hanson LA, Weiss ST, Celedon JC. Maternal history, sensitization to allergens, and current wheezing, rhinitis, and eczema among children in Costa Rica. Pediatr Pulmonol. 2002;33:237–43.

    PubMed  Google Scholar 

  32. Kurukulaaratchy RJ, Matthews S, Arshad SH. Relationship between childhood atopy and wheeze: what mediates wheezing in atopic phenotypes? Ann Allergy Asthma Immunol. 2006;97:84–91.

    PubMed  Google Scholar 

  33. Hamada K, Suzaki Y, Goldman A, Ning YY, Goldsmith C, Palecanda A, et al. Allergen-independent maternal transmission of asthma susceptibility. J Immunol. 2003;170:1683–9.

    CAS  PubMed  Google Scholar 

  34. Liu CA, Wang CL, Chuang H, Ou CY, Hsu TY, Yang KD. Prediction of elevated cord blood IgE levels by maternal IgE levels, and the neonate’s gender and gestational age. Chang Gung Med J. 2003;26:561–9.

    PubMed  Google Scholar 

  35. Raby BA, Klanderman B, Murphy A, Mazza S, Camargo Jr CA, Silverman EK, et al. A common mitochondrial haplogroup is associated with elevated total serum IgE levels. J Allergy Clin Immunol. 2007;120:351–8.

    CAS  PubMed  Google Scholar 

  36. Clifton VL, Davies M, Moore V, Wright IM, Ali Z, Hodyl NA. Developmental perturbation induced by maternal asthma during pregnancy: the short- and long-term impacts on offspring. J Pregnancy. 2012;2012:741613. Epub 2012 Jul 8.

    PubMed Central  PubMed  Google Scholar 

  37. Zifa E, Daniil Z, Skoumi E, Stavrou M, Papadimitriou K, Terzenidou M, et al. Mitochondrial genetic background plays a role in increasing risk to asthma. Mol Biol Rep. 2012;39: 4697–708.

    CAS  PubMed  Google Scholar 

  38. Schauberger EM, Ewart SL, Arshad SH, Huebner M, Karmaus W, Holloway JW, et al. Identification of ATPAF1 as a novel candidate gene for asthma in children. J Allergy Clin Immunol. 2011;128:753–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Fukuda T, Mochida S, Fukushima Y, Makino S. Detection of allergen-induced genes in peripheral blood mononuclear cells of patients with allergic asthma using subtractive hybridization. J Allergy Clin Immunol. 1995;96:1076–82.

    CAS  PubMed  Google Scholar 

  40. Polonikov AV, Ivanov VP, Solodilova MA, Kozhukhov MA, Panfilov VI, Bulgakova VI. Polymorphism -930A > G of the cytochrome b gene is a novel genetic marker of predisposition to bronchial asthma. Ter Arkh. 2009;81:31–5.

    CAS  PubMed  Google Scholar 

  41. Schmuczerova J, Brdicka R, Dostal M, Sram RJ, Topinka J. Genetic variability of HVRII mtDNA in cord blood and respiratory morbidity in children. Mutat Res. 2009;666:1–7.

    CAS  PubMed  Google Scholar 

  42. Jones M, Mitchell P, Wang JJ, Sue C. MELAS A3243G mitochondrial DNA mutation andage related maculopathy. Am J Ophthalmol. 2004;138:1051–3.

    CAS  PubMed  Google Scholar 

  43. Shanske AL, Shanske S, Silvestri G, Tanji K, Wertheim D, Lipper S. MELAS point mutation with unusual clinical presentation. Neuromuscul Disord. 1993;3:191–3.

    CAS  PubMed  Google Scholar 

  44. Finsterer J. Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR)mutation. Acta Neurol Scand. 2007;116:1–14.

    CAS  PubMed  Google Scholar 

  45. Marchetti P, Castedo M, Susin SA, Zamzami N, Hirsch T, Macho A, et al. Mitochondrial permeability transition is a central coordinating event of apoptosis. J Exp Med. 1996;184: 1155–60.

    CAS  PubMed  Google Scholar 

  46. Elias JA, Zhu Z, Chupp G, Homer RJ. Airway remodeling in asthma. J Clin Invest. 1999;104:1001–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Elias JA, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z. New insights into the pathogenesis of asthma. J Clin Invest. 2003;111:291–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Konga DB, Kim Y, Hong SC, Roh YM, Lee CM, Kim KY, et al. Oxidative stress and antioxidant defenses in asthmatic murine model exposed to printer emissions and environmental tobacco smoke. J Environ Pathol Toxicol Oncol. 2009;28:325–40.

    CAS  PubMed  Google Scholar 

  49. Chodaczek G, Bacsi A, Dharajiya N, Sur S, Hazra TK, Boldogh I. Ragweed pollen-mediated IgE-independent release of biogenic amines from mast cells via induction of mitochondrial dysfunction. Mol Immunol. 2009;46:2505–14.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Xu W, Comhair SAA, Janocha AJ, Mavrakis LA, Erzurum SC. Alteration of nitric oxide synthesis related to abnormal cellular bioenergetics in asthmatic airway epithelium. Am J Respir Crit Care Med. 2010;181:A1436.

    Google Scholar 

  51. Ramakrishna R, Edwards JS, McCulloch A, Palsson BO. Flux balance analysis of mitochondrial energy metabolism: consequences of systemic stoichiometric constraints. Am J Physiol Regul Integr Comp Physiol. 2001;280:R695–704.

    CAS  PubMed  Google Scholar 

  52. Weller PF, Ackerman SJ, Smith JA. Eosinophil granule cationic proteins: major basic protein is distinct from the smaller subunit of eosinophil peroxidase. Leukoc Biol. 1988;43:1–4.

    CAS  Google Scholar 

  53. Wood LG, Gibson PG, Garg ML. Biomarkers of lipid peroxidation, airway inflammation and asthma. Eur Respir J. 2003;21:177–86.

    CAS  PubMed  Google Scholar 

  54. Macmillan-Crow LA, Jahangir DL. Invited review: manganese superoxide dismutase in disease. Free Radic Res. 2001;34:325–36.

    CAS  PubMed  Google Scholar 

  55. Comhair SA, Ricci KS, Arroliga M, Lara AR, Dweik RA, Song W, et al. Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma. Am J Respir Crit Care Med. 2005;172:306–13.

    PubMed Central  PubMed  Google Scholar 

  56. Larsen NB, Rasmussen M, Rasmussen LJ. Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion. 2005;5:89–108.

    CAS  PubMed  Google Scholar 

  57. Ames BN, Shigenaga MK, Hagen TM. Mitochondrial decay in aging. Biochim Biophys Acta. 1995;1271:165–70.

    PubMed  Google Scholar 

  58. Schewe T. 15-lipoxygenase-1: a prooxidant enzyme. Biol Chem. 2002;383:365–74.

    CAS  PubMed  Google Scholar 

  59. Géminard C, de Gassart A, Vidal M. Reticulocyte maturation: mitoptosis and exosome release. Biocell. 2002;26:205–15.

    PubMed  Google Scholar 

  60. Chanez P, Bonnans C, Chavis C, Vachier I. 15-lipoxygenase: a Janus enzyme? Am J Respir Cell Mol Biol. 2002;27:655–8.

    CAS  PubMed  Google Scholar 

  61. Andersson CK, Claesson HE, Rydell-Törmänen K, Swedmark S, Hällgren A, Erjefält JS. Mice lacking 12/15-lipoxygenase have attenuated airway allergic inflammation and remodeling. Am J Respir Cell Mol Biol. 2008;39:648–56.

    CAS  PubMed  Google Scholar 

  62. Hajek AR, Lindley AR, Favoreto Jr S, Carter R, Schleimer RP, Kuperman DA. 12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels. J Allergy Clin Immunol. 2008;122:633–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Ricciardolo FL. cNOS-iNOS paradigm and arginase in asthma. Trends Pharmacol Sci. 2003;24:560–1.

    CAS  PubMed  Google Scholar 

  64. Mabalirajan U, Ahmad T, Leishangthem GD, Joseph DA, Dinda AK, Agrawal A, et al. Beneficial effects of high dose of L-Arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma. J Allergy Clin Immunol. 2010;125:626–35.

    CAS  PubMed  Google Scholar 

  65. Shiva S, Crawford JH, Ramachandran A, Ceaser EK, Hillson T, Brookes PS, et al. Mechanisms of the interaction of nitroxyl with mitochondria. Biochem J. 2004;379:359–66.

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Capaldi RA. Structure and function of cytochrome oxidase. Annu Rev Biochem. 1992;59: 569–96.

    Google Scholar 

  67. Szabó C, Ischiropoulos H, Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov. 2007;6:662–80.

    PubMed  Google Scholar 

  68. Ahmad T, Mabalirajan U, Ghosh B, Agrawal A. Altered assymetric dimethyl arginine metabolism in bronchial epithelium of allergically inflamed lungs. Am J Resp cell Mol Biol. 2010;42:3–8.

    CAS  Google Scholar 

  69. Mabalirajan U, Ahmad T, Leishangthem G, Dinda AK, Agrawal A, Ghosh B. L-arginine reduces mitochondrial dysfunction and epithelial injury in murine allergic airway inflammation. Int Immunopharmacol. 2010;10:1514–9.

    CAS  PubMed  Google Scholar 

  70. Scott JA, North ML, Rafii M, Huang H, Pencharz P, Subbarao P, Belik J, Grasemann H. Asymmetric dimethylarginine is increased in asthma. Am J Respir Crit Care Med. 2011;184:779–85.

    CAS  PubMed  Google Scholar 

  71. Lacza Z, Pankotai E, Csordás A, Gero D, Kiss L, Horváth EM, et al. Mitochondrial NO and reactive nitrogen species production: does mtNOS exist? Nitric Oxide. 2006;14:162–8.

    CAS  PubMed  Google Scholar 

  72. Sud N, Wells SM, Sharma S, Wiseman DA, Wilham J, Black SM. Asymmetric dimethylarginine inhibits HSP90 activity in pulmonary arterial endothelial cells: role of mitochondrial dysfunction. Am J Physiol Cell Physiol. 2008;294:1407–18.

    Google Scholar 

  73. Wells SM, Buford MC, Migliaccio CT, Holian A. Elevated asymmetric dimethylarginine alters lung function and induces collagen deposition in mice. Am J Respir Cell Mol Biol. 2009;40:179–88.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Wells SM, Holian A. Asymmetric dimethylarginine induces oxidative and nitrosative stress in murine lung epithelial cells. Am J Respir Cell Mol Biol. 2007;36:520–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Robinson NC. Functional binding of cardiolipin to cytochrome c oxidase. J Bioenerg Biomembr. 1993;25:153–63.

    CAS  PubMed  Google Scholar 

  76. Ott M, Zhivotovsky B, Orrenius S. Role of cardiolipin in cytochrome c release from mitochondria. Cell Death Differ. 2007;14:1243–7.

    CAS  PubMed  Google Scholar 

  77. Comhair SA, Xu W, Ghosh S, Thunnissen FB, Almasan A, Calhoun WJ, et al. Superoxide dismutase inactivation in pathophysiology of asthmatic airway remodeling and reactivity. Am J Pathol. 2005;166:663–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Grigoraş CC, Grigoraş A, Mihăescu T, Floarea-Stra A, Cozma L, Vereş L. Expression of the Bax proapoptotic factor in asthmatic patients. Pneumologia. 2009;58:8–12.

    PubMed  Google Scholar 

  79. Kampf C, Relova AJ, Sandler S, Roomans GM. Effects of TNF-alpha, IFN-gamma and IL-beta on normal human bronchial epithelial cells. Eur Respir J. 1999;14:84–91.

    CAS  PubMed  Google Scholar 

  80. Shi ZQ, Feng Y, Hou YK, Liu T, Xiu QY. A study of interferon-gamma induced airway mucous cell apoptosis and its mechanisms. Zhonghua Jie He He Hu Xi Za Zhi. 2005;28:160–3.

    PubMed  Google Scholar 

  81. Chang KC, Lo CW, Fan TC, Chang MD, Shu CW, Chang CH, et al. TNF-alpha mediates eosinophil cationic protein-induced apoptosis in BEAS-2B cells. BMC Cell Biol. 2010;11:6.

    PubMed Central  PubMed  Google Scholar 

  82. Serradell MC, Guasconi L, Masih DT. Involvement of a mitochondrial pathway and key role of hydrogen peroxide during eosinophil apoptosis induced by excretory-secretory products from Fasciola hepatica. Mol Biochem Parasitol. 2009;163:95–106.

    CAS  PubMed  Google Scholar 

  83. Gardai SJ, Hoontrakoon R, Goddard CD, Day BJ, Chang LY, Henson PM, et al. Oxidant-mediated mitochondrial injury in eosinophil apoptosis: enhancement by glucocorticoids and inhibition by granulocyte-macrophage colony-stimulating factor. J Immunol. 2003;170: 556–66.

    CAS  PubMed  Google Scholar 

  84. Dewson G, Cohen GM, Wardlaw AJ. Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c release, and activation of caspases in human eosinophils. Blood. 2001;98:2239–47.

    CAS  PubMed  Google Scholar 

  85. Druilhe A, Létuvé S, Pretolani M. Glucocorticoid-induced apoptosis in human eosinophils: mechanisms of action. Apoptosis. 2003;8:481–95.

    CAS  PubMed  Google Scholar 

  86. Walsh GM, Sexton DW, Blaylock MG. Corticosteroids, eosinophils and bronchial epithelial cells: new insights into the resolution of inflammation in asthma. J Endocrinol. 2003;178(1): 37–43.

    CAS  PubMed  Google Scholar 

  87. Cruz AA, Bousquet PJ. The unbearable cost of severe asthma in underprivileged populations. Allergy. 2009;64(3):319–21.

    CAS  PubMed  Google Scholar 

  88. Holgate ST, Lackie P, Wilson S, Roche W, Davies D. Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma. Am J Respir Crit Care Med. 2000;162:S113–7.

    CAS  PubMed  Google Scholar 

  89. O’Sullivan MP, Tyner JW, Holtzman MJ. Apoptosis in the airways: another balancing act in the epithelial program. Am J Respir Cell Mol Biol. 2003;29:3–7.

    PubMed  Google Scholar 

  90. Holgate ST. The inflammation-repair cycle in asthma: the pivotal role of the airway epithelium. Clin Exp Allergy. 1998;28 Suppl 5:97–103.

    CAS  PubMed  Google Scholar 

  91. Holgate ST, Holloway J, Wilson S, Bucchieri F, Puddicombe S, Davies DE. Epithelial-mesenchymal communication in the pathogenesis of chronic asthma. Proc Am Thorac Soc. 2004;1:93–8.

    CAS  PubMed  Google Scholar 

  92. Davies DE, Holgate ST. Asthma: the importance of epithelial mesenchymal communication in pathogenesis. Inflammation and the airway epithelium in asthma. Int J Biochem Cell Biol. 2002;34:1520–6.

    CAS  PubMed  Google Scholar 

  93. Zimmermann N, King NE, Laporte J, Yang M, Mishra A, Pope SM, et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest. 2003;111:1863–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Delwing D, Delwing D, Chiarani F, Kurek AG, Wyse AT. Proline reduces brain cytochrome c oxidase: prevention by antioxidants. Int J Dev Neurosci. 2007;25:17–22.

    CAS  PubMed  Google Scholar 

  95. Trian T, Benard G, Begueret H, Rossignol R, Girodet PO, Ghosh D, et al. Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma. J Exp Med. 2007;204:3173–81.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Lee I, Salomon AR, Ficarro S, Mathes I, Lottspeich F, Grossman LI, et al. cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity. J Biol Chem. 2005;280:6094–100.

    CAS  PubMed  Google Scholar 

  97. Pelaia G, Di Paola ED, De Sarro G, Marsico SA. Is the mitochondrial benzodiazepine receptor involved in the control of airway smooth muscle tone? Gen Pharmacol. 1997;28:495–8.

    CAS  PubMed  Google Scholar 

  98. Ten Broeke R, Blalock JE, Nijkamp FP, Folkerts G. Calcium sensors as new therapeutic targets for asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 2004;34: 170–6.

    CAS  PubMed  Google Scholar 

  99. Duchen MR. Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signalling and cell death. J Physiol. 1999;516:1–17.

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Herrington J, Park YB, Babcock DF, Hille B. Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal chromaffin cells. Neuron. 1996;16:219–28.

    CAS  PubMed  Google Scholar 

  101. Peng TI, Jou MJ. Oxidative stress caused by mitochondrial calcium overload. Ann N Y Acad Sci. 2010;1201:183–8.

    CAS  PubMed  Google Scholar 

  102. Feissner RF, Skalska J, Gaum WE, Sheu SS. Crosstalk signaling between mitochondrial Ca2+ and ROS. Front Biosci. 2009;14:1197–218.

    CAS  Google Scholar 

  103. Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R. The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet. 2010;19:111–21.

    CAS  PubMed  Google Scholar 

  104. Folkerts G, Busse WW, Nijkamp FP, Sorkness R, Gern JE. Virus induced airway hyperresponsiveness and asthma. Am J Respir Crit Care Med. 1998;157:1708–20.

    CAS  PubMed  Google Scholar 

  105. You D, Becnel D, Wang K, Ripple M, Daly M, Cormier SA. Exposure of neonates to respiratory syncytial virus is critical in determining subsequent airway response in adults. Respir Res. 2006;7:107.

    PubMed Central  PubMed  Google Scholar 

  106. Punyadarsaniya D, Liang CH, Winter C, Petersen H, Rautenschlein S, Hennig-Pauka I, et al. Infection of differentiated porcine airway epithelial cells by influenza virus: differential susceptibility to infection by porcine and avian viruses. PLoS One. 2011;6:e28429.

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122:669–82.

    CAS  PubMed  Google Scholar 

  108. Qi B, Huang Y, Rowe D, Halliday G. VISA–a pass to innate immunity. Int J Biochem Cell Biol. 2007;39:287–91.

    CAS  PubMed  Google Scholar 

  109. Tang ED, Wang CY. MAVS self-association mediates antiviral innate immune signaling. J Virol. 2009;83:3420–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Seth RB, Sun L, Chen ZJ. Antiviral innate immunity pathways. Cell Res. 2006;16:141–7.

    CAS  PubMed  Google Scholar 

  111. Rehwinkel J, Reis e Sousa C. RIGorous detection: exposing virus through RNA sensing. Science. 2010;327:284–6.

    CAS  PubMed  Google Scholar 

  112. Land JM, Morgan-Hughes JA, Hargreaves I, Heales SJ. Mitochondrial disease: a historical, biochemical, and London perspective. Neurochem Res. 2004;29:483–91.

    CAS  PubMed  Google Scholar 

  113. Szeto HH. Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J. 2006;8:521–31.

    Google Scholar 

  114. Armstrong JS. Mitochondrial medicine: pharmacological targeting of mitochondria in disease. Br J Pharmacol. 2007;151:1154–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Szewczyk A, Wojtczak L. Mitochondria as a pharmacological target. Pharmacol Rev. 2002;54:101–27.

    CAS  PubMed  Google Scholar 

  116. Barnhill AE, Brewer MT, Carlson SA. Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of host mitochondrial components. Antimicrob Agents Chemother. 2012;56:4046–51.

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, et al. Mitochondrial transfer from bone-marrow derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med. 2012;18:759–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Jones CP, Rankin SM. Bone marrow-derived stem cells and respiratory disease. Chest. 2011;140:205–11.

    CAS  PubMed  Google Scholar 

  119. Kapoor S, Patel SA, Kartan S, Axelrod D, Capitle E, Rameshwar P. Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy-induced asthma. J Allergy Clin Immunol. 2012;129:1094–101.

    CAS  PubMed  Google Scholar 

  120. Mabalirajan U, Dinda AK, Sharma SK, Ghosh B. Esculetin restores mitochondrial dysfunction and reduces allergic asthma features in experimental murine model. J Immunol. 2009;183:2059–67.

    CAS  PubMed  Google Scholar 

  121. Mabalirajan U, Aich J, Sharma SK, Ghosh B. Effects of vitamin E on mitochondrial dysfunction and asthma features in an experimental allergic murine model. J Appl Physiol. 2009;107:1285–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Ahmad T, Mabalirajan U, Sharma A, Ghosh B, Agrawal A. Simvastatin improves epithelial dysfunction and airway hyperresponsiveness: from ADMA to asthma. Am J Resp Cell Mol Biol. 2011;44:531–9.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Molecular Immunogenetics Laboratory, Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India

    Ulaganathan Mabalirajan MBBS, PhD & Anurag Agrawal MD, PhD

  2. Molecular Immunogenetics Laboratory, CSIR- Institute of Genomics and Integrative Biology, Delhi University Campus (North), Mall Road, Delhi, 110007, India

    Balaram Ghosh PhD, FNA, FNASc, FASc

Authors
  1. Ulaganathan Mabalirajan MBBS, PhD
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  2. Anurag Agrawal MD, PhD
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  3. Balaram Ghosh PhD, FNA, FNASc, FASc
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Corresponding author

Correspondence to Balaram Ghosh PhD, FNA, FNASc, FASc .

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Editors and Affiliations

  1. Department of Pharmaology and Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

    Viswanathan Natarajan

  2. Division of Allergy, Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, College of Medicine, Ohio State University Wexner, Medical Center, Columbus, Ohio, USA

    Narasimham L. Parinandi

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Mabalirajan, U., Agrawal, A., Ghosh, B. (2014). Mitochondrion: A Missing Link in Asthma Pathogenesis. In: Natarajan, V., Parinandi, N. (eds) Mitochondrial Function in Lung Health and Disease. Respiratory Medicine, vol 15. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0829-5_3

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  • DOI: https://doi.org/10.1007/978-1-4939-0829-5_3

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