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Cell Biology and Toxicology

, Volume 35, Issue 6, pp 493–502 | Cite as

Mitochondrial dysfunction and chronic lung disease

  • Tingting Fang
  • Manni Wang
  • Hengyi XiaoEmail author
  • Xiawei WeiEmail author
Review

Abstract

The functions of body gradually decrease as the age increases, leading to a higher frequency of incidence of age-related diseases. Diseases associated with aging in the respiratory system include chronic obstructive pulmonary disease (COPD), IPF (idiopathic pulmonary fibrosis), asthma, lung cancer, and so on. The mitochondrial dysfunction is not only a sign of aging, but also is a disease trigger. This article aims to explain mitochondrial dysfunction as an aging marker, and its role in aging diseases of lung. We also discuss whether the mitochondria can be used as a target for the treatment of aging lung disease.

Keywords

Mitochondrial dysfunction Chronic lung diseases mtROS mtDNA Mitochondrial dynamic 

Notes

Acknowledgments

TT-F, MN-W, XW-W, and HY-X are supported by Lab of Aging Research and Nanotoxicology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital.TT-F and MN-W are co-first authors.

Funding

This work is supported by the National Key Research and Development Program of China (No. 2016YFA0201402) and the National Natural Science Foundation of China (No. 81602492).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Alonso A, Martin P, Albarran C, Aguilera B, Garcia O, Guzman A, et al. Detection of somatic mutations in the mitochondrial DNA control region of colorectal and gastric tumors by heteroduplex and single-strand conformation analysis. Electrophoresis. 1997;18(5):682–5.PubMedGoogle Scholar
  2. Andrianifahanana M, Hernandez DM, Yin X, Kang J-H, Jung M-Y, Wang Y, et al. Profibrotic up-regulation of glucose transporter 1 by TGF-β involves activation of MEK and mammalian target of rapamycin complex 2 pathways. FASEB J. 2016;30(11):3733–44.  https://doi.org/10.1096/fj.201600428R.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ashrafi G, Schwarz TL. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ. 2013;20(1):31–42.PubMedGoogle Scholar
  4. Bensinger SJ, Christofk HR. New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol. 2012;23:352–61.PubMedGoogle Scholar
  5. Bonner MR, Shen M, Liu CS, Divita M, He X, Lan Q. Mitochondrial DNA content and lung cancer risk in Xuan Wei, China. Lung Cancer. 2009;63(3):331–4.PubMedGoogle Scholar
  6. Bueno M, Lai YC, Romero Y, Brands J, St. Croix CM, Kamga C, et al. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J Clin Invest. 2015;125(2):521–38.PubMedPubMedCentralGoogle Scholar
  7. Burgart LJ, Zheng J, Shu Q, Strickler JG, Shibata D. Somatic mitochondrial mutation in gastric cancer. Am J Pathol. 1995;147(4):1105–11.PubMedPubMedCentralGoogle Scholar
  8. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11(2):85–95.PubMedGoogle Scholar
  9. Chatterjee A, Dasgupta S, Sidransky D. Mitochondrial subversion in cancer. Cancer Prev Res (Phila). 2011;4(5):638–54.Google Scholar
  10. Chen Y, Zhang J, Lin Y, Lei Q, Guan KL, Zhao S, et al. Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS. EMBO Rep. 2011;12(6):534–41.PubMedPubMedCentralGoogle Scholar
  11. Chiche J, Rouleau M, Gounon P, Brahimi-Horn MC, Pouysségur J, Mazure NM. Hypoxic enlarged mitochondria protect cancer cells from apoptotic stimuli. J Cell Physiol. 2010;222(3):648–57.PubMedGoogle Scholar
  12. Cho SJ, Moon J-S, Lee C-M, Choi AMK, Stout-Delgado HW. Glucose transporter 1-dependent glycolysis is increased during aging-related lung fibrosis, and phloretin inhibits lung fibrosis. Am J Respir Cell Mol Biol. 2017;56(4):521–31.  https://doi.org/10.1165/rcmb.2016-0225OC.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Dasgupta S, Soudry E, Mukhopadhyay N, Shao C, Yee J, Lam S, et al. Mitochondrial DNA mutations in respiratory complex-I in never-smoker lung cancer patients contribute to lung cancer progression and associated with EGFR gene mutation. J Cell Physiol. 2012;227(6):2451–60.PubMedPubMedCentralGoogle Scholar
  14. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012;393(7):547–64.PubMedPubMedCentralGoogle Scholar
  15. Du G, Sun T, Zhang Y, et al. The mitochondrial dysfunction plays an important role in urethane-induced lung carcinogenesis. Eur J Pharmacol. 2013;715(1–3):395–404.PubMedGoogle Scholar
  16. Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM, et al. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science. 2000;287(5460):2017–9.PubMedGoogle Scholar
  17. Gasparre G, Kurelac I, Capristo M, et al. A mutation threshold distinguishes the anti-tumorigenic effects of the mitochondrial gene MTND1, an Oncojanus function. Cancer Res. 2011;71:6220e9.Google Scholar
  18. Gibson GJ, Loddenkemper R, Lundbäck B, Sibille Y. Respiratory health and disease in Europe: the new European lung white book. Eur Respir J. 2013;42(3):559–63.PubMedGoogle Scholar
  19. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12:9–22.PubMedGoogle Scholar
  20. Habano W, Sugai T, Nakamura SI, Uesugi N, Yoshida T, Sasou S. Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma. Gastroenterology. 2000;118(5):835–41.PubMedGoogle Scholar
  21. Hawkins A, Guttentag SH, Deterding R, Funkhouser WK, Goralski JL, Chatterjee S, et al. A non-BRICHOS SFTPC mutant (SP-CI73T) linked to interstitial lung disease promotes a late block in macroautophagy disrupting cellular proteostasis and mitophagy. Am J Phys Lung Cell Mol Phys. 2015;308(1):L33–47.Google Scholar
  22. Hosgood HD 3rd, Liu CS, Rothman N, et al. Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study. Carcinogenesis. 2010;31(5):847–9.PubMedPubMedCentralGoogle Scholar
  23. Jiang Y, Wang X, Hu D. Mitochondrial alterations during oxidative stress in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2017;Volume 12:1153–62.Google Scholar
  24. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell. 2005;18:283–93.PubMedPubMedCentralGoogle Scholar
  25. Justet A, Laurent-Bellue A, Thabut G, et al. [<sup>18</sup>F]FDG PET/CT predicts progression-free survival in patients with idiopathic pulmonary fibrosis. Respir Res. 2017;18(1):74.PubMedPubMedCentralGoogle Scholar
  26. Kageyama S, Sou YS, Uemura T, Kametaka S, Saito T, Ishimura R, et al. Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway. J Biol Chem. 2014;289(36):24944–55.PubMedPubMedCentralGoogle Scholar
  27. Khatri S, Yepiskoposyan H, Gallo CA, Tandon P, Plas DR. FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1. J Biol Chem. 2010;285:15960–5.PubMedPubMedCentralGoogle Scholar
  28. Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys. 2007;462(2):245–53.PubMedPubMedCentralGoogle Scholar
  29. Kim SJ, Cheresh P, Jablonski RP, et al. Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage. Free Radic Biol Med. 2016.Google Scholar
  30. Kottmann RM, Kulkarni AA, Smolnycki KA, Lyda E, Dahanayake T, Salibi R, et al. Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-β. Am J Respir Crit Care Med. 2012;186(8):740–51.  https://doi.org/10.1164/rccm.201201-0084OC.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kubli DA, Gustafsson ÅB. Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res. 2012;111(9):1208–21.PubMedPubMedCentralGoogle Scholar
  32. Li J, Jiang P, Robinson M, Lawrence TS, Sun Y. AMPK-beta1 subunit is a p53-independent stress responsive protein that inhibits tumor cell growth upon forced expression. Carcinogenesis. 2003;24(5):827–34.PubMedGoogle Scholar
  33. Li B, Gordon GM, Du CH, Xu J, Du W. Specific killing of Rb mutant cancer cells by inactivating TSC2. Cancer Cell. 2010;17(5):469–80.PubMedPubMedCentralGoogle Scholar
  34. Liu X, Chen Z. The pathophysiological role of mitochondrial oxidative stress in lung diseases. J Transl Med. 2017;15(1):207.PubMedPubMedCentralGoogle Scholar
  35. Maher TM. Aerobic glycolysis and the Warburg effect. An unexplored realm in the search for fibrosis therapies? Am J Respir Crit Care Med. 2015;192(12):1407–9.PubMedPubMedCentralGoogle Scholar
  36. Máximo V, Soares P, Seruca R, Sobrinho-Simões M. Comments on: mutations in mitochondrial control region DNA in gastric tumours of Japanese patients, Tamura, et al. Eur J Cancer 1999, 35, 316-319. Eur J Cancer. 1999;35(9):1407–8.PubMedGoogle Scholar
  37. Mercado N, Ito K, Barnes PJ. Accelerated ageing of the lung in COPD: new concepts. Thorax. 2015;70(5):482–9.PubMedGoogle Scholar
  38. Mizumura K, Cloonan SM, Nakahira K, Bhashyam AR, Cervo M, Kitada T, et al. Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD. J Clin Invest. 2014;124(9):3987–4003.PubMedPubMedCentralGoogle Scholar
  39. Mora AL, Bueno M, Rojas M. Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis. J Clin Invest. 2017;127(2):405–14.PubMedPubMedCentralGoogle Scholar
  40. Nam HS, Izumchenko E, Dasgupta S, Hoque MO. Mitochondria in chronic obstructive pulmonary disease and lung cancer: where are we now? Biomark Med. 2017;11(6):475–89.PubMedPubMedCentralGoogle Scholar
  41. Noguera A, Batle S, Miralles C, Iglesias J, Busquets X, MacNee W, et al. Enhanced neutrophil response in chronic obstructive pulmonary disease. Thorax. 2001;56:432e7.Google Scholar
  42. Ott M, Gogvadze V, Orrenius S, et al. Mitochondria, oxidative stress and cell death. Apoptosis. 2007;12:913e22.Google Scholar
  43. Parsons DW, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–12.PubMedPubMedCentralGoogle Scholar
  44. Penta JS, Johnson FM, Wachsman JT, et al. Mitochondrial DNA in human malignancy. Mutat Res. 2001;488:119e33.Google Scholar
  45. Piantadosi CA, Suliman HB. Mitochondrial Dysfunction in Lung Pathogenesis. Annu Rev Physiol. 2017Google Scholar
  46. Picca A, Lezza AMS, Leeuwenburgh C, et al. Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets. Int J Mol Sci. 2017;18(5).PubMedCentralGoogle Scholar
  47. Plas DR, Thompson CB. Akt-dependent transformation: there is more to growth than just surviving. Oncogene. 2005;24(50):7435–42.PubMedGoogle Scholar
  48. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE Biological and chemical approaches to diseases of proteostasis deficiency Annu Rev Biochem 2009Google Scholar
  49. Prakash YS, Pabelick CM, Sieck GC. Mitochondrial dysfunction in airway disease. Chest. 2017;152(3):618–26.PubMedPubMedCentralGoogle Scholar
  50. Rabinovich RA, Bastos R, Ardite E, Llinas L, Orozco-Levi M, Gea J, et al. Mitochondrial dysfunction in COPD patients with low body mass index. Eur Respir J. 2007;29(4):643–50.PubMedGoogle Scholar
  51. Rangarajan S, Bernard K, Thannickal VJ. Mitochondrial Dysfunction in Pulmonary Fibrosis. Ann Am Thorac Soc. 2017;14(Supplement_5):S383–8.PubMedPubMedCentralGoogle Scholar
  52. Richter C, Gogvadze V, Laffranchi R, et al. Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta. 1995;1271:67e74.Google Scholar
  53. Roberts ER, Thomas KJ. The role of mitochondria in the development and progression of lung cancer. Comput Struct Biotechnol J. 2013;6:e201303019.PubMedPubMedCentralGoogle Scholar
  54. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005;434(7029):113–8.  https://doi.org/10.1038/nature03354.CrossRefPubMedGoogle Scholar
  55. Ryu C, Sun H, Gulati M, Herazo-Maya JD, Chen Y, Osafo-Addo A, et al. Extracellular mitochondrial DNA is generated by fibroblasts and predicts death in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2017;196(12):1571–81.PubMedPubMedCentralGoogle Scholar
  56. Sahin E, Colla S, Liesa M, Moslehi J, Müller FL, Guo M, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 2011;470(7334):359–65.  https://doi.org/10.1038/nature09787.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Servais S, Couturier K, Koubi H, et al. Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria. Free Radic Biol Med. 2003;35(1):24–32.PubMedGoogle Scholar
  58. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 2009;9(8):563–75.PubMedPubMedCentralGoogle Scholar
  59. Shidara Y, Yamagata K, Kanamori T, et al. Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res. 2005;65:1655e63.Google Scholar
  60. Sinthupibulyakit C, Ittarat W, St Clair WH, St Clair DK. p53 protects lung cancer cells against metabolic stress. Int J Oncol. 2010;37(6):1575–81.PubMedPubMedCentralGoogle Scholar
  61. Sisson TH, Mendez M, Choi K, Subbotina N, Courey A, Cunningham A, et al. Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis. Am J Respir Crit Care Med. 2010;181(3):254–63.PubMedGoogle Scholar
  62. Soulitzis N, Neofytou E, Psarrou M, Anagnostis A, Tavernarakis N, Siafakas N, et al. Downregulation of lung mitochondrial prohibitin in COPD. Respir Med. 2012;106(7):954–61.PubMedGoogle Scholar
  63. Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458:719–24.PubMedPubMedCentralGoogle Scholar
  64. Suzuki M, Toyooka S, Miyajima K, Iizasa T, Fujisawa T, Bekele NB, et al. Alterations in the mitochondrial displacement loop in lung cancers. Clin Cancer Res. 2003;9(15):5636–41.PubMedGoogle Scholar
  65. Taanman J-W. The mitochondrial genome: structure, transcription, translation and replication. Biochim Biophys Acta. 1999;1410:103e23.Google Scholar
  66. Tang BL. Sirt1 and the mitochondria. Mol Cell. 2016;39(2):87–95.  https://doi.org/10.14348/molcells.2016.2318.CrossRefGoogle Scholar
  67. Thannickal VJ. Mechanistic links between aging and lung fibrosis. Biogerontology. 2013;14(6):609-15Mora AL, Rojas M, Pardo a, Selman M. emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease. Nat Rev Drug Discov. 2017;16(11):755–72.Google Scholar
  68. the international Cancer genome consortium. International network of cancer genome projects. Nature. 2010;464:993–8.PubMedCentralGoogle Scholar
  69. Thomas AQ, Lane K, Phillips J 3rd, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med. 2002;165(9):1322–8.PubMedGoogle Scholar
  70. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging,and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359–407.  https://doi.org/10.1146/annurev.genet.39.110304.095751.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Warburg O. On respiratory impairment in cancer cells. Science. 1956;124(3215):269–70.PubMedGoogle Scholar
  72. Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation and impairment of antioxidant enzymes in aging. Proc Soc Exp Biol Med. 2002:671e82.Google Scholar
  73. West AP. Mitochondrial dysfunction as a trigger of innate immune responses and inflammation. Toxicology. 2017.Google Scholar
  74. World Health Organization World and Europe Detailed Mortality Databases. http://data.euro.who.int/dmdb/. Date last accessed: June 20, 2013.
  75. World Health Organization. World Health Statistics 2011.Geneva,World HealthOrganization,2011http://wwwwhoint/entity/whosis/whostat/EN_WHS2011_Fullpdf. Date last accessed: June 20, 2013.
  76. Xu CX, Jin H, Shin JY, Kim JE, Cho MH. Roles of protein kinase B/Akt in lung cancer. Front Biosci (Elite Ed). 2010.Google Scholar
  77. Xu Y, Mizuno T, Sridharan A, Du Y, Guo M, Tang J, et al. Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis. JCI Insight. 2016;1(20):e90558.  https://doi.org/10.1172/jci.insight.90558.CrossRefPubMedPubMedCentralGoogle Scholar
  78. Yang Ai SS, Hsu K, Herbert C, Cheng Z, Hunt J, Lewis CR, et al. Mitochondrial DNA mutations in exhaled breath condensate of patients with lung cancer. Respir Med. 2013;107(6):911–8.PubMedGoogle Scholar
  79. Yoo DG, Song YJ, Cho EJ, Lee SK, Park JB, Yu JH, et al. Alteration of APE1/ref-1 expression in non-small cell lung cancer: the implications of impaired extracellular superoxide dismutase and catalase antioxidant systems. Lung Cancer. 2008;60(2):277–84.PubMedGoogle Scholar
  80. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12(1):9–14.PubMedPubMedCentralGoogle Scholar
  81. Yu YP, Yu G, Tseng G, Cieply K, Nelson J, Defrances M, et al. Glutathione peroxidase 3, deleted or methylated in prostate cancer, suppresses prostate cancer growth and metastasis. Cancer Res. 2007;67(17):8043–50.PubMedGoogle Scholar
  82. Yu W, Dittenhafer-Reed KE, Denu JM. SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status. J Biol Chem. 2012;287(17):14078–86.PubMedPubMedCentralGoogle Scholar
  83. Yue L, Yao H. Mitochondrial dysfunction in inflammatory responses and cellular senescence: pathogenesis and pharmacological targets for chronic lung diseases. Br J Pharmacol. 2016;173(15):2305–18.PubMedPubMedCentralGoogle Scholar
  84. Zamzami N, Kroemer G. The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol. 2001;2:67e71.Google Scholar
  85. Zank DC, Bueno M, Mora AL, Rojas M. Idiopathic pulmonary fibrosis: aging, mitochondrial dysfunction, and cellular bioenergetics. Front Med (Lausanne). 2018;5.Google Scholar
  86. Zeng Z, Cheng S, Chen H, Li Q, Hu Y, Wang Q, et al. Activation and overexpression of Sirt1 attenuates lung fibrosis via P300. Biochem Biophys Res Commun. 2017;486(4):1021–6.  https://doi.org/10.1016/j.bbrc.2017.03.155.CrossRefPubMedGoogle Scholar
  87. Zhang L, Wang W, Zhu B, Wang X. Epithelial Mitochondrial Dysfunction in Lung Disease. Adv Exp Med Biol. 2017.Google Scholar
  88. Zhang Z, Cheng X, Yue L, Cui W, Zhou W, Gao J, et al. Molecular pathogenesis in chronic obstructive pulmonary disease and therapeutic potential by targeting AMP-activated protein kinase. J Cell Physiol. 2018;233(3):1999–2006.PubMedGoogle Scholar

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Lab of Aging Research and Nanotoxicology, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China HospitalSichuan University and National Collaborative Innovation CenterChengduChina

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