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Mitochondrial Function in Lung Health and Disease

  • Luis Puente-MaestuEmail author
  • Jorge Chancafe-Morgan
Chapter
  • 728 Downloads
Part of the Respiratory Medicine book series (RM, volume 15)

Abstract

The mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling and cell death. The mitochondrion is able to sense PO2 throughout the progressive reduction of cytochrome c with increasing hypoxia. This information is converted into an increase in reactive oxygen species production at complex III that acts as cell signal. Such signal is believed to be responsible for phenomena such as hypoxic vasoconstriction, activation of HIF, and internalization of the sodium-potassium pump of the alveolar epithelium. Mitochondrial DNA mutations are frequent in cancer cells. These mutations lead to an impaired oxidative metabolism and to decreased susceptibility to apoptosis. These two features are needed for survival of the cancer cell. There are two major signaling pathways of apoptosis and one of them involves the mitochondria. Apoptosis plays an important role in most lung diseases in two different ways. First, failure to clear unwanted cells by apoptosis will prolong the inflammation; second, excessive apoptosis may cause diseases. Finally the skeletal muscle dysfunction associated with COPD involves the loss of oxidative capacity, mainly due to the loss of mitochondrial density.

Keywords

Apoptosis Mitochondria Permeability transition pore Electron transport chain Reactive oxygen species Hypoxic vasoconstriction Cell signaling Skeletal muscle dysfunction Remodeling HIF Mitochondrial DNA mutations 

Abbreviations

AMPK

AMP-activated protein kinase

Apaf1

Apoptotic protease activating factor 1

ATP

Adenosine triphosphate

Bax

Bcl-2-associated X protein

Bcl-2

B-cell lymphoma 2

CD95

Cluster of differentiation 95

Cl

Chlorine

CoA

Coenzyme A

COPD

Chronic obstructive pulmonary disease

COX

Cytochrome c oxidase

CS

Citrate synthase

DNA

Deoxyribonucleic acid

ENa

Amiloride-sensitive sodium channels

FADD

Fas-associated death domain protein

Fas

FAS receptor (FasR) also known as apoptosis antigen 1

FasL

Fas ligand

H2O2

Hydrogen peroxide

HIF

Hypoxia-inducible factor

HO-1

Heme oxygenase 1

IMS

Intermembrane space

IPF

Idiopathic pulmonary fibrosis

mDNA

Mitochondrial DNA

MPT

Mitochondrial permeability transition

Na

Sodium

NRS

Nitrosative reactive species

O2

Molecular oxygen

p53

Tumor protein 53

PHD2

Prolyl hydroxylase domain-containing protein 2

PO2

Oxygen pressure

PTP

Permeability transition pore

roGFP

Mutated variant of green fluorescent protein

ROS

Reactive oxygen species

SDH

Succinate dehydrogenase

SMD

Skeletal muscle dysfunction

SOD

Superoxide dismutase

TNF

Tumor necrosis factor

TRADD

TNF receptor-associated death domain

References

  1. 1.
    Henze K, Martin W. Evolutionary biology: essence of mitochondria. Nature. 2003;426: 127–8.PubMedGoogle Scholar
  2. 2.
    McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr Biol. 2006;16:R551–60.PubMedGoogle Scholar
  3. 3.
    Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 1996;334:1469–70.PubMedGoogle Scholar
  4. 4.
    Gusarova GA, Dada LA, Kelly AM, et al. Alpha1-AMP-activated protein kinase regulates hypoxia-induced Na, K-ATPase endocytosis via direct phosphorylation of protein kinase C zeta. Mol Cell Biol. 2009;29:3455–64.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Comellas AP, Dada LA, Lecuona E, et al. Hypoxia-mediated degradation of Na, K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system. Circ Res. 2006;98:1314–22.PubMedGoogle Scholar
  6. 6.
    Vadasz I, Dada LA, Briva A, et al. AMP-activated protein kinase regulates CO2-induced alveolar epithelial dysfunction in rats and human cells by promoting Na, K-ATPase endocytosis. J Clin Invest. 2008;118:752–62.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Semenza GL. Oxygen homeostasis. Wiley Interdiscip Rev Syst Biol Med. 2010;2:336–61.PubMedGoogle Scholar
  8. 8.
    Skuli N, Liu L, Runge A, et al. Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis. Blood. 2009;114:469–77.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Huang LE, Gu J, Schau M, Bunn HF. Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 1998;95:7987–92.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Appelhoff RJ, Tian YM, Raval RR, et al. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J Biol Chem. 2004;279:38458–65.PubMedGoogle Scholar
  11. 11.
    Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci U S A. 1998;95:11715–20.PubMedCentralPubMedGoogle Scholar
  12. 12.
    Chandel NS, McClintock DS, Feliciano CE, et al. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem. 2000;275:25130–8.PubMedGoogle Scholar
  13. 13.
    Guzy RD, Hoyos B, Robin E, et al. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 2005;1:401–8.PubMedGoogle Scholar
  14. 14.
    Mansfield KD, Guzy RD, Pan Y, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab. 2005;1:393–9.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Schumacker PT. Lung cell hypoxia: role of mitochondrial reactive oxygen species signaling in triggering responses. Proc Am Thorac Soc. 2011;8:477–84.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Evans AM, Hardie DG, Peers C, Mahmoud A. Hypoxic pulmonary vasoconstriction: mechanisms of oxygen-sensing. Curr Opin Anaesthesiol. 2011;24:13–20.PubMedCentralPubMedGoogle Scholar
  17. 17.
    Mark EA, Ward JP. Hypoxic pulmonary vasoconstriction – invited article. Adv Exp Med Biol. 2009;648:351–60.Google Scholar
  18. 18.
    Rumsey WL, Schlosser C, Nuutinen EM, Robiolio M, Wilson DF. Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J Biol Chem. 1990;265:15392–402.PubMedGoogle Scholar
  19. 19.
    Wilson DF, Erecinska M. Effect of oxygen concentration on cellular metabolism. Chest. 1985;88:229S–32.PubMedGoogle Scholar
  20. 20.
    Wilson DF, Rumsey WL, Green TJ, Vanderkooi JM. The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen concentration. J Biol Chem. 1988;263:2712–8.PubMedGoogle Scholar
  21. 21.
    Guzy RD, Schumacker PT. Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Exp Physiol. 2006;91:807–19.PubMedGoogle Scholar
  22. 22.
    Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem. 1998;273:11619–24.PubMedGoogle Scholar
  23. 23.
    Vanden Hoek TL, Becker LB, Shao Z, Li C, Schumacker PT. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem. 1998;273:18092–8.PubMedGoogle Scholar
  24. 24.
    Robin E, Guzy RD, Loor G, et al. Oxidant stress during simulated ischemia primes cardiomyocytes for cell death during reperfusion. J Biol Chem. 2007;282:19133–43.PubMedGoogle Scholar
  25. 25.
    Waypa GB, Guzy R, Mungai PT, et al. Increases in mitochondrial reactive oxygen species trigger hypoxia-induced calcium responses in pulmonary artery smooth muscle cells. Circ Res. 2006;99:970–8.PubMedGoogle Scholar
  26. 26.
    Becker LB, Vanden Hoek TL, Shao ZH, Li CQ, Schumacker PT. Generation of superoxide in cardiomyocytes during ischemia before reperfusion. Am J Physiol. 1999;277:H2240–6.PubMedGoogle Scholar
  27. 27.
    Dooley CT, Dore TM, Hanson GT, Jackson WC, Remington SJ, Tsien RY. Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators. J Biol Chem. 2004;279:22284–93.PubMedGoogle Scholar
  28. 28.
    Hanson GT, Aggeler R, Oglesbee D, et al. Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators. J Biol Chem. 2004;279:13044–53.PubMedGoogle Scholar
  29. 29.
    Waypa GB, Marks JD, Guzy R, et al. Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells. Circ Res. 2010;106:526–35.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Puente-Maestu L, Tejedor A, Lazaro A, et al. Site of mitochondrial ROS production in skeletal muscle of COPD and its relationship with exercise oxidative stress. Am J Respir Cell Mol Biol. 2012;47:358–62.PubMedGoogle Scholar
  31. 31.
    Brunelle JK, Bell EL, Quesada NM, et al. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab. 2005;1:409–14.PubMedGoogle Scholar
  32. 32.
    Connolly MJ, Aaronson PI. Cell redox state and hypoxic pulmonary vasoconstriction: recent evidence and possible mechanisms. Respir Physiol Neurobiol. 2010;174:165–74.PubMedGoogle Scholar
  33. 33.
    Waypa GB, Chandel NS, Schumacker PT. Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res. 2001;88:1259–66.PubMedGoogle Scholar
  34. 34.
    Waypa GB, Marks JD, Mack MM, Boriboun C, Mungai PT, Schumacker PT. Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes. Circ Res. 2002;91:719–26.PubMedGoogle Scholar
  35. 35.
    Waypa GB, Schumacker PT. Hypoxia-induced changes in pulmonary and systemic vascular resistance: where is the O2 sensor? Respir Physiol Neurobiol. 2010;174:201–11.PubMedCentralPubMedGoogle Scholar
  36. 36.
    Kroemer G. Mitochondria in cancer. Oncogene. 2006;25:4630–2.PubMedGoogle Scholar
  37. 37.
    King A, Selak MA, Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene. 2006;25:4675–82.PubMedGoogle Scholar
  38. 38.
    Robey RB, Hay N. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene. 2006;25:4683–96.PubMedGoogle Scholar
  39. 39.
    Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene. 2006;25: 4647–62.PubMedGoogle Scholar
  40. 40.
    Chatterjee A, Mambo E, Sidransky D. Mitochondrial DNA mutations in human cancer. Oncogene. 2006;25:4663–74.PubMedGoogle Scholar
  41. 41.
    Guzy RD, Sharma B, Bell E, Chandel NS, Schumacker PT. Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol Cell Biol. 2008;28:718–31.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Dasgupta S, Yung RC, Westra WH, Rini DA, Brandes J, Sidransky D. Following mitochondrial footprints through a long mucosal path to lung cancer. PLoS One. 2009;4:e6533.PubMedCentralPubMedGoogle Scholar
  43. 43.
    Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999;341(Pt 2):233–49.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305: 626–9.PubMedGoogle Scholar
  45. 45.
    Zamzami N, Brenner C, Marzo I, Susin SA, Kroemer G. Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins. Oncogene. 1998;16:2265–82.PubMedGoogle Scholar
  46. 46.
    Cheng WC, Berman SB, Ivanovska I, et al. Mitochondrial factors with dual roles in death and survival. Oncogene. 2006;25:4697–705.PubMedGoogle Scholar
  47. 47.
    Brenner C, Grimm S. The permeability transition pore complex in cancer cell death. Oncogene. 2006;25:4744–56.PubMedGoogle Scholar
  48. 48.
    Alirol E, Martinou JC. Mitochondria and cancer: is there a morphological connection? Oncogene. 2006;25:4706–16.PubMedGoogle Scholar
  49. 49.
    Cereghetti GM, Scorrano L. The many shapes of mitochondrial death. Oncogene. 2006;25: 4717–24.PubMedGoogle Scholar
  50. 50.
    Moll UM, Marchenko N, Zhang XK. p53 and Nur77/TR3 - transcription factors that directly target mitochondria for cell death induction. Oncogene. 2006;25:4725–43.PubMedGoogle Scholar
  51. 51.
    Fontenay M, Cathelin S, Amiot M, Gyan E, Solary E. Mitochondria in hematopoiesis and hematological diseases. Oncogene. 2006;25:4757–67.PubMedGoogle Scholar
  52. 52.
    Kim KH, Park JY, Jung HJ, Kwon HJ. Identification and biological activities of a new antiangiogenic small molecule that suppresses mitochondrial reactive oxygen species. Biochem Biophys Res Commun. 2011;404:541–5.PubMedGoogle Scholar
  53. 53.
    Kuwano K. Epithelial cell apoptosis and lung remodeling. Cell Mol Immunol. 2007;4: 419–29.PubMedGoogle Scholar
  54. 54.
    Matute-Bello G, Liles WC, Frevert CW, et al. Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits. Am J Physiol Lung Cell Mol Physiol. 2001;281:L328–35.PubMedGoogle Scholar
  55. 55.
    Kroemer G, Reed JC. Mitochondrial control of cell death. Nat Med. 2000;6:513–9.PubMedGoogle Scholar
  56. 56.
    Chen G, Goeddel DV. TNF-R1 signaling: a beautiful pathway. Science. 2002;296:1634–5.PubMedGoogle Scholar
  57. 57.
    Bardales RH, Xie SS, Schaefer RF, Hsu SM. Apoptosis is a major pathway responsible for the resolution of type II pneumocytes in acute lung injury. Am J Pathol. 1996;149:845–52.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Guinee Jr D, Brambilla E, Fleming M, et al. The potential role of BAX and BCL-2 expression in diffuse alveolar damage. Am J Pathol. 1997;151:999–1007.PubMedCentralPubMedGoogle Scholar
  59. 59.
    Guinee Jr D, Fleming M, Hayashi T, et al. Association of p53 and WAF1 expression with apoptosis in diffuse alveolar damage. Am J Pathol. 1996;149:531–8.PubMedCentralPubMedGoogle Scholar
  60. 60.
    Fujita M, Kuwano K, Kunitake R, et al. Endothelial cell apoptosis in lipopolysaccharide-induced lung injury in mice. Int Arch Allergy Immunol. 1998;117:202–8.PubMedGoogle Scholar
  61. 61.
    Ward NS, Waxman AB, Homer RJ, et al. Interleukin-6-induced protection in hyperoxic acute lung injury. Am J Respir Cell Mol Biol. 2000;22:535–42.PubMedGoogle Scholar
  62. 62.
    Waxman AB, Einarsson O, Seres T, et al. Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation. J Clin Invest. 1998;101:1970–82.PubMedCentralPubMedGoogle Scholar
  63. 63.
    Paine III R, Wilcoxen SE, Morris SB, et al. Transgenic overexpression of granulocyte macrophage-colony stimulating factor in the lung prevents hyperoxic lung injury. Am J Pathol. 2003;163:2397–406.PubMedCentralPubMedGoogle Scholar
  64. 64.
    Hiromatsu T, Yajima T, Matsuguchi T, et al. Overexpression of interleukin-15 protects against Escherichia coli-induced shock accompanied by inhibition of tumor necrosis factor-alpha-induced apoptosis. J Infect Dis. 2003;187:1442–51.PubMedGoogle Scholar
  65. 65.
    Kuwano K, Kunitake R, Kawasaki M, et al. P21Waf1/Cip1/Sdi1 and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1996;154:477–83.PubMedGoogle Scholar
  66. 66.
    Uhal BD, Joshi I, Hughes WF, Ramos C, Pardo A, Selman M. Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung. Am J Physiol. 1998;275:L1192–9.PubMedGoogle Scholar
  67. 67.
    Barbas-Filho JV, Ferreira MA, Sesso A, Kairalla RA, Carvalho CR, Capelozzi VL. Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP). J Clin Pathol. 2001;54:132–8.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Kuwano K, Miyazaki H, Hagimoto N, et al. The involvement of Fas-Fas ligand pathway in fibrosing lung diseases. Am J Respir Cell Mol Biol. 1999;20:53–60.PubMedGoogle Scholar
  69. 69.
    Kuwano K. Involvement of epithelial cell apoptosis in interstitial lung diseases. Intern Med. 2008;47:345–53.PubMedGoogle Scholar
  70. 70.
    Bucchieri F, Puddicombe SM, Lordan JL, et al. Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis. Am J Respir Cell Mol Biol. 2002;27:179–85.PubMedGoogle Scholar
  71. 71.
    Cohen L, Xueping E, Tarsi J, et al. Epithelial cell proliferation contributes to airway remodeling in severe asthma. Am J Respir Crit Care Med. 2007;176:138–45.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Aoshiba K, Yokohori N, Nagai A. Alveolar wall apoptosis causes lung destruction and emphysematous changes. Am J Respir Cell Mol Biol. 2003;28:555–62.PubMedGoogle Scholar
  73. 73.
    Henson PM, Cosgrove GP, Vandivier RW. State of the art. Apoptosis and cell homeostasis in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3:512–6.PubMedCentralPubMedGoogle Scholar
  74. 74.
    Kang MJ, Homer RJ, Gallo A, et al. IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation. J Immunol. 2007;178:1948–59.PubMedGoogle Scholar
  75. 75.
    Carnevali S, Petruzzelli S, Longoni B, et al. Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2003;284: L955–63.PubMedGoogle Scholar
  76. 76.
    Henson PM, Vandivier RW, Douglas IS. Cell death, remodeling, and repair in chronic obstructive pulmonary disease? Proc Am Thorac Soc. 2006;3:713–7.PubMedCentralPubMedGoogle Scholar
  77. 77.
    van der Toorn M, Slebos DJ, de Bruin HG, et al. Cigarette smoke-induced blockade of the mitochondrial respiratory chain switches lung epithelial cell apoptosis into necrosis. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1211–8.PubMedGoogle Scholar
  78. 78.
    Slebos DJ, Ryter SW, van der Toorn TM, et al. Mitochondrial localization and function of heme oxygenase-1 in cigarette smoke-induced cell death. Am J Respir Cell Mol Biol. 2007;36:409–17.PubMedCentralPubMedGoogle Scholar
  79. 79.
    Jakobsson P, Jorfeldt L, Henriksson J. Metabolic enzyme activity in the quadriceps femoris muscle in patients with severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;151:374–7.PubMedGoogle Scholar
  80. 80.
    Maltais F, LeBlanc P, Whittom F, et al. Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD. Thorax. 2000;55:848–53.PubMedCentralPubMedGoogle Scholar
  81. 81.
    Puente-Maestu L, Tena T, Trascasa C, et al. Training improves muscle oxidative capacity and oxygenation recovery kinetics in patients with chronic obstructive pulmonary disease. Eur J Appl Physiol. 2003;88:580–7.PubMedGoogle Scholar
  82. 82.
    Sauleda J, Garcia-Palmer FJ, Palou A, Agusti AG. Metabolic enzyme activity in the quadriceps femoris muscle in patients with severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152:1137–8.PubMedGoogle Scholar
  83. 83.
    Rabinovich RA, Bastos R, Ardite E, et al. Mitochondrial dysfunction in COPD patients with low body mass index. Eur Respir J. 2007;29:643–50.PubMedGoogle Scholar
  84. 84.
    Puente-Maestu L, Perez-Parra J, Godoy R, et al. Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients. Eur Respir J. 2009;33:1045–52.PubMedGoogle Scholar
  85. 85.
    Picard M, Godin R, Sinnreich M, et al. The mitochondrial phenotype of peripheral muscle in chronic obstructive pulmonary disease: disuse or dysfunction? Am J Respir Crit Care Med. 2008;178:1040–7.PubMedGoogle Scholar
  86. 86.
    Naimi AI, Bourbeau J, Perrault H, et al. Altered mitochondrial regulation in quadriceps muscles of patients with COPD. Clin Physiol Funct Imaging. 2011;31:124–31.PubMedGoogle Scholar
  87. 87.
    Gosker HR, Hesselink MK, Duimel H, Ward KA, Schols AM. Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD. Eur Respir J. 2007;30:73–9.PubMedGoogle Scholar
  88. 88.
    Puente-Maestu L, Lazaro A, Tejedor A, et al. Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD. Thorax. 2011;66:121–7.PubMedGoogle Scholar
  89. 89.
    den Hoed M, Hesselink MK, van Kranenburg GP, Westerterp KR. Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity. J Appl Physiol. 2008;105:561–8.Google Scholar
  90. 90.
    Hoppeler H, Weibel ER. Limits for oxygen and substrate transport in mammals. J Exp Biol. 1998;201:1051–64.PubMedGoogle Scholar
  91. 91.
    Maltais F, LeBlanc P, Simard C, et al. Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;154: 442–7.PubMedGoogle Scholar
  92. 92.
    McKeough ZJ, Alison JA, Bye PT, et al. Exercise capacity and quadriceps muscle metabolism following training in subjects with COPD. Respir Med. 2006;100:1817–25.PubMedGoogle Scholar
  93. 93.
    Saltin B. The interplay between peripheral and central factors in the adaptive response to exercise and training. Ann N Y Acad Sci. 1977;301:224–31.PubMedGoogle Scholar
  94. 94.
    Doucet M, Debigare R, Joanisse DR, et al. Adaptation of the diaphragm and the vastus lateralis in mild-to-moderate COPD. Eur Respir J. 2004;24:971–9.PubMedGoogle Scholar
  95. 95.
    Levine S, Gregory C, Nguyen T, et al. Bioenergetic adaptation of individual human diaphragmatic myofibers to severe COPD. J Appl Physiol. 2002;92:1205–13.PubMedGoogle Scholar
  96. 96.
    Wijnhoven JH, Janssen AJ, van Kuppevelt TH, Rodenburg RJ, Dekhuijzen PN. Metabolic capacity of the diaphragm in patients with COPD. Respir Med. 2006;100:1064–71.PubMedGoogle Scholar
  97. 97.
    Sanchez J, Bastien C, Medrano G, Riquet M, Derenne JP. Metabolic enzymatic activities in the diaphragm of normal men and patients with moderate chronic obstructive pulmonary disease. Bull Eur Physiopathol Respir. 1984;20:535–40.PubMedGoogle Scholar
  98. 98.
    Ribera F, N’Guessan B, Zoll J, et al. Mitochondrial electron transport chain function is enhanced in inspiratory muscles of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:873–9.PubMedGoogle Scholar
  99. 99.
    Couillard A, Koechlin C, Cristol JP, Varray A, Prefaut C. Evidence of local exercise-induced systemic oxidative stress in chronic obstructive pulmonary disease patients. Eur Respir J. 2002;20:1123–9.PubMedGoogle Scholar
  100. 100.
    Pinho RA, Chiesa D, Mezzomo KM, et al. Oxidative stress in chronic obstructive pulmonary disease patients submitted to a rehabilitation program. Respir Med. 2007;101:1830–5.PubMedGoogle Scholar
  101. 101.
    Ji LL. Exercise, oxidative stress, and antioxidants. Am J Sports Med. 1996;24:S20–4.PubMedGoogle Scholar
  102. 102.
    Barreiro E, Gea J, Matar G, Hussain SN. Expression and carbonylation of creatine kinase in the quadriceps femoris muscles of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2005;33:636–42.PubMedGoogle Scholar
  103. 103.
    Koechlin C, Couillard A, Simar D, et al. Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2004;169:1022–7.PubMedGoogle Scholar
  104. 104.
    Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88:1243–76.PubMedCentralPubMedGoogle Scholar
  105. 105.
    Tonkonogi M, Walsh B, Svensson M, Sahlin K. Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress. J Physiol. 2000;528(Pt 2):379–88.PubMedCentralPubMedGoogle Scholar
  106. 106.
    Dean RT, Fu S, Stocker R, Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J. 1997;324:1–18.PubMedCentralPubMedGoogle Scholar
  107. 107.
    Nagasawa T, Hatayama T, Watanabe Y, Tanaka M, Niisato Y, Kitts DD. Free radical-mediated effects on skeletal muscle protein in rats treated with Fe-nitrilotriacetate. Biochem Biophys Res Commun. 1997;231:37–41.PubMedGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Respiratory Medicine/NeumologíaHospital General Universitario Gregorio Marañón- Universidad Complutense de MadridMadridSpain

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