Functional state of mitochondria in chronic respiratory diseases

Introduction. Chronic respiratory diseases are one of the most common types of non-communicable diseases and are an important problem of our time. The induction of oxidative stress, chronic inflammation and hypoxia, which underlie the pathogenesis of chronic diseases of the bronchopulmonary system, can be determined at the cellular and molecular level by impaired mitochondrial functioning.

Aim. This review is devoted to the prospects for assessing the functional state of mitochondria as a fine indicator of the course of chronic respiratory diseases.

Results. The data of domestic and foreign sources on the most important parameters of mitochondrial functioning in normal and chronic bronchopulmonary pathology were analyzed. It has been shown that mitochondria are highly sensitive to changes in both exogenous and endogenous homeostasis. Functional parameters of mitochondria, the level of mitochondrial reactive oxygen species, mitochondrial membrane potential, and fatty acid composition of mitochondrial membranes can be used as diagnostic and prognostic criteria for chronic respiratory diseases. The data presented in the review indicate the need for further studies of the functional state of mitochondria in chronic bronchopulmonary pathology.

1. WHO. Chronic respiratory diseases (asthma, COPD). 15 July 2019. Available at: https://www.who.int/westernpacific/health-topics/chronic-respiratory-diseases

2. Global initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2021. Available at: http://www.ginasthma.org

3. Global initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2021. Available at: http://www.goldcopd.org

4. Prozorovskaya Yu.I., Kostyushok N.Ya., Golubtsova G.A., Pavlyuchenko I.I., Gusaruk L.R. [Aspects of metabolic shifts in patients with chronic obstructive pulmonary disease of various phenotypes]. Mezhdunarodniy nauchno-issledovatel'skiy zhurnal = International Research Journal 2021; (8-2):123−129 (in Russian). https://doi.org/10.23670/IRJ.2021.110.8.060

5. Zhou W.C., Qu J., Xie S.Y., Sun Y., Yao H.W. Mitochondrial Dysfunction in Chronic Respiratory Diseases: Implications for the Pathogenesis and Potential Therapeutics. Oxid. Med. Cell. Longev. 2021; 2021: 5188306. https://doi.org/10.1155/2021/5188306

6. Haji G., Wiegman C.H., Michaeloudes C., Patel M.S., Curtis K., Bhavsar P., Polkey M.I., Adcock I.M., Chung K.F. Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease. Respir. Res. 2020; 21(1):262. https://doi.org/10.1186/s12931-020-01527-5

7. Gvozdjáková A., editor. Mitochondrial Medicine. Mitochondrial Metabolism, Diseases, Diagnosis and Therapy. Springer; 2008. ISBN: 978-1-4020-6714-3

8. Scheffler I.E. Mitochondria. 2nd ed. NY: A John Wiley & Sons Inc.; 2008. ISBN: 978-0-470-04073-7

9. Berdanier C.D., editor. Mitochondria in Health and Disease.1st ed.� Boca Raton: Taylor and Francis CRC Press; 2005. ISBN: 0-8247-5442-5

10. Aghapour M., Remels A.H.V., Pouwels S.D., Bruder D., Hiemstra P.S., Cloonan S.M., Heijink I.H. Mitochondria: at the crossroads of regulating lung epithelial cell function in chronic obstructive pulmonary disease. Am. J. Physiol. Lung Cell. Mol. Physiol. 2020; 318(1):L149–L164. https://doi.org/10.1152/ajplung.00329.2019

11. Caldeira D.A.F., Weiss D.J., Rocco P.R.M., Silva P.L., Cruz F.F. Mitochondria in Focus: From Function to Therapeutic Strategies in Chronic Lung Diseases. Front. Immunol. 2021; 12: 782074. doi: 10.3389/fimmu.2021.782074

12. Cloonan S.M, Kim K., Esteves P., Trian T., Barnes P.J. Mitochondrial Dysfunction in Lung Ageing and Disease. Eur. Respir. Rev. 2020; 29(157): 200165 https://doi.org/10.1183/16000617.0165-2020

13. Andreyev A.Y., Kushnareva Y.E., Starkova N.N., Starkov A.A. Metabolic ROS signaling: to immunity and beyond. Biochemistry (Mosc). 2020; 85(12):1650–1667 (in Russian). https://doi.org/10.1134/S0006297920120160

14. Zorov D.B., Juhaszova M., Sollott S.J. Mitochondrial reactive oxygen species (ROS) and ROS induced ROS release. Physiol. Rev. 2014; 94(3):909 950. https://doi.org/10.1152/physrev.00026.2013

15. Dard L., Blanchard W., Hubert C., Lacombe D. Rossignol R. Mitochondrial functions and rare diseases. Mol. Aspects Med. 2020; 71:100842. https://doi.org/10.1016/j.mam. 2019.100842

16. Cloonan S.M., Choi A.M. Mitochondria in lung disease. J. Clin. Invest. 2016; 126(3):809–820. https://doi.org/10.1172/JCI81113

17. Sena L.A., Li S., Jairaman A., Prakriya M., Ezponda T., Hildeman D.A., Wang C.R., Schumacker P.T., Licht J.D., Perlman H., Bryce P.J., Chandel N.S. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 2013; 38(2):225–236. https://doi.org/10.1016/j.immuni.2012.10.020

18. Okoye I., Wang L., Pallmer K., Richter K., Ichimura T., Haas R., Crouse J., Choi O., Heathcote D., Lovo E., Mauro C., Abdi R., Oxenius A., Rutschmann S., Ashton-Rickardt P.G. The protein LEM promotes CD8⁺ T cell immunity through effects on mitochondrial respiration. Science 2015; 348(6238):995–1001. https://doi.org/10.1126/science.aaa7516

19. Berod L., Friedrich C., Nandan A., Freitag J., Hagemann S., Harmrolfs K., Sandouk A., Hesse C., Castro C.N., Bähre H., Tschirner S.K., Gorinski N., Gohmert M., Mayer C.T., Huehn J., Ponimaskin E., Abraham W.R., Müller R., Lochner M., Sparwasser T. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat. Med. 2014; 20(11):1327–1333. https://doi.org/10.1038/nm.3704

20. Weinberg S.E., Sena L.A., Chandel N.S. Mitochondria in the regulation of innate and adaptive immunity. Immunity 2015; 42(3):406 417. https://doi.org/10.1016/j.immuni.2015.02.002

21. Gill T., Levine A.D. Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction. J. Biol. Chem. 2013; 288(36):26246 26255. https://doi.org/10.1074/jbc.M113.476895

22. Chodaczek G., Bacsi A., Dharajiya N., Sur S., Hazra T.K., Boldogh I. Ragweed pollen-mediated IgE-independent release of biogenic amines from mast cells via induction of mitochondrial dysfunction. Mol. Immunol. 2009; 46(13):2505–2514. https://doi.org/10.1016/j.molimm.2009.05.023

23. Antonyuk M.V., Mineeva E.E., Knyshova V.V., Urenko A.V., Vitkina T.I., Novgorodtseva T.P., Gvozdenko T.A. [Features of immune response in different phenotypes of chronic obstructive pulmonary disease]. Medical Immunology (Russia) 2022; 24(1):109–120 (in Russian). https://doi.org/10.15789/1563-0625-FOI-2321

24. Sidletskaya K.A., Vitkina T.I., Denisenko Y.K., Mineeva E.E. Role of Toll-Like Receptor 2 in Regulation of THelper Immune Response in Chronic Obstructive Pulmonary Disease. Can. Respir. J. 2021; 2021:5596095. https://doi.org/10.1155/2021/5596095

25. Vitkina T., Sidletskaya K., Denisenko Yu. Expression of CD282+/CD284+ on blood granulocytes and its relationship to cytokine status in patients with stable chronic obstructive pulmonary disease. Eur. Respir. J. Suppl. 2021; 58(S65):PA3423.

26. Kalinina E.P., Vitkina T.I., Knyshova V.V., Fedoseeva E.A., Novgorodtseva T.P., Gvozdenko T.A. [Clinical and immunological comparisons in Th-dependent immune response mechanisms among patients with chronic obstructive pulmonary disease]. Medical Immunology (Russia) 2018; 20(6):855–864 (in Russian). https://doi.org/10.15789/1563-0625-2018-6-855-864

27. Kalinina E., Denisenko Y., Vitkina T., Lobanova E., Novgorodtseva T., Antonyuk M., Gvozdenko T., Knyshova V., Nazarenko A. The Mechanisms of the Regulation of Immune Response in Patients with Comorbidity of Chronic Obstructive Pulmonary Disease and Asthma. Can. Respir. J. 2016; 2016:4503267. https://doi.org/10.1155/2016/4503267

28. Denisenko Yu.K., Vitkina T.I., Kondratyeva E.V., Zhukova N.V., Nazarenko A.V. [Modification of the composition of fatty acids in membranes of mitochondria of platelets in patients with chronic non-obstructive bronchitis]. Health. Medical Ecology. Science 2014; 2(56):59–61 (in Russian). Available at: http://yadi.sk/d/OzhZjBl8SaPYj

29. Denisenko Yu.K., Vitkina T.I., Novgorodtseva T.P., Kondratʹeva E.V., Zhukova N.V., Borshchev P.V. [Fatty acid spectrum of mitochondrial thrombocytes membranes in patients with chronic non-obstructive bronchitis]. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration 2013; (50):34–38 (in Russian).

30. Denisenko Yu.K., Novgorodceva T.P., Vitkina T.I., Antonyuk M.V., Bocharova N.V. [The fatty acid composition of the mitochondrial membranes of platelets in chronic obstructive pulmonary disease]. Klinicheskaia meditsina = Clinical Medicine (Russian Journal) 2018; 96(4):343–347 (in Russian). https://doi.org/10.18821/0023-2149-2018-96-4-343-347

31. Denisenko Yu.K., Novgorodceva T.P., Vitkina T.I., Antonyuk M.V., Zhukova N.V. [Mitochondrial dysfunction in chronic obstructive pulmonary disease]. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration 2016; (60):28–33 (in Russian).

32. Denisenko Yu.K., Novgorodtseva T.P., Vitkina T.I., Zhukova N.V., Gvozdenko T.A., Knyshova V.V. [The response of platelet and leukocyte mitochondria of healthy residents on the impact of atmospheric microparticles]. Russian Journal of Physiology 2019; 105(1):111–120 (in Russian). https://doi.org/10.1134/S0869813919010023

33. Denisenko Yu.K., Novgorodtseva T.P., Kondrat'eva E.V., Zhukova N.V., Antonyuk M.V., Knyshova V.V., Mineeva E.E. [Morpho-functional characteristics of blood cell mitochondria in bronchial asthma]. Klin. Med. (Mosk) 2015; 93(10):47–51 (in Russian). PMID: 26964466

34. Kondratieva E.V., Lobanova E.G. [The influence of ozone on the membrane potential of mitochondria of thrombocytes]. Medical Almanac 2013; (3):58–59 (in Russian).

35. Lobanova E.G., Kondrat'eva E.V. Measurement of mitochondrial membrane potential in leukocyte suspension by fluorescent spectroscopy. Bull. Exp. Biol. Med. 2014; 157(2):288–290. https://doi.org/10.1007/s10517-014-2547-4

36. Lobanova E.G., Kondratiyeva E.V., Mineeva E.E., Karaman Yu.K. [The membrane potential of mitochondria of thrombocytes in patients with chronic obstructive disease of lungs]. Klin. Lab. Diagn. 2014; (6):13–16 (in Russian). PMID: 25335394

37. Golokhvast K., Vitkina T., Gvozdenko T., Kolosov V., Yankova V., Kondratieva E., Gorkavaya A., Nazarenko A., Chaika V., Romanova T., Karabtsov A., Perelman J., Kiku P., Tsatsakis A. Impact of atmospheric microparticles on the development of oxidative stress in healthy city/industrial seaport resident. Oxid. Med. Cell. Longev. 2015; 2015:412173. doi 10.1155/2015/412173

38. Zorova L.D., Popkov V.A., Plotnikov E.Y., Silachev D.N., Pevzner I.B., Jankauskas S.S., Babenko V.A., Zorov S.D., Balakireva A.V., Juhaszova M., Sollott S.J., Zorov D.B. Mitochondrial membrane potential. Anal. Biochem. 2018; 552:50–59. https://doi.org/10.1016/j.ab.2017.07.009

39. Teodoro J., Palmeira C.M., Rolo A.P. Mitochondrial Membrane Potential (ΔΨ) Fluctuations Associated with the Metabolic States of Mitochondria. Methods Mol. Biol. 2018;1782:109–119. https://doi.org/10.1007/978-1-61779-382-0_6

40. Bagkos G., Koufopoulos K., Piperi C. A new model for mitochondrial membrane potential production and storage. Med. Hypotheses 2014; 83(2):175–181. https://doi.org/10.1016/j.mehy.2014.05.001

41. Zhou T., Hu Y., Wang Y., Sun C., Zhong Y., Liao J., Wang G. Fine particulate matter (PM2.5) aggravates apoptosis of cigarette-inflamed bronchial epithelium in vivo and vitro. Environ. Pollut. 2019; 248:1–9. https://doi.org/10.1016/j.envpol.2018.11.054

42. [Chronic obstructive pulmonary disease. Clinical recommendations]. Moscow; 2021 (in Russian). Available at: https://cr.minzdrav.gov.ru/schema/603_2

43. Tulen C.B.M., Snow S.J., Leermakers P.A., Kodavanti U.P., van Schooten F.J., Opperhuizen A., Remels A.H.V. Acrolein inhalation acutely affects the regulation of mitochondrial metabolism in rat lung. Toxicology 2022; 469:153129. https://doi.org/10.1016/j.tox.2022.153129

44. Hara H., Araya J., Ito S., Kobayashi K., Takasaka N., Yoshii Y., Wakui H., Kojima J., Shimizu K., Numata T., Kawaishi M., Kamiya N., Odaka M., Morikawa T., Kaneko Y., Nakayama K., Kuwano K. Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence. Am. J. Physiol. Lung Cell. Mol. Physiol. 2013; 305(10):L737–746. https://doi.org/10.1152/ajplung.00146.2013

45. Hoffmann R.F., Zarrintan S., Brandenburg S.M., Kol A., de Bruin H.G., Jafari S., Dijk F., Kalicharan D., Kelders M., Gosker H.R., Ten Hacken N.H., van der Want J.J., van Oosterhout A.J., Heijink I.H. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells. Respir. Res. 2013; 14(1):97. https://doi.org/10.1186/1465-9921-14-97

46. Ahmad T., Sundar I.K., Lerner C.A., Gerloff J., Tormos A.M., Yao H., Rahman I. Impaired mitophagy leads to cigarette smoke stress-induced cellular senescence: implications for chronic obstructive pulmonary disease. FASEB J. 2015; 29(7):2912–2929. https://doi.org/10.1096/fj.14-268276

47. Mao J., Li Y., Li S., Li J., Tian Y., Feng S., Liu X., Bian Q., Li J., Hu Y., Zhang L., Ji H. Bufei Jianpi Granules Reduce Quadriceps Muscular Cell Apoptosis by Improving Mitochondrial Function in Rats with Chronic Obstructive Pulmonary Disease. Evid. Based Complement. Alternat. Med. 2019; 2019:1216305. https://doi.org/10.1155/2019/1216305

48. Kosmider B., Lin C.R., Karim L., Tomar D., Vlasenko L., Marchetti N., Bolla S., Madesh M., Criner G.J., Bahmed K. Mitochondrial dysfunction in human primary alveolar type II cells in emphysema. EBioMedicine 2019; 46:305–316. https://doi.org/10.1016/j.ebiom.2019.07.063

49. Wiegman C.H., Michaeloudes C., Haji G., Narang P., Clarke C.J., Russell K.E., Bao W., Pavlidis S., Barnes P.J., Kanerva J., Bittner A., Rao N., Murphy M.P., Kirkham P.A., Chung K.F., Adcock I.M. COPDMAP. Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 2015; 136(3):769–780. https://doi.org/10.1016/j.jaci.2015.01.046

50. Wu K., Luan G., Xu Y., Shen S., Qian S., Zhu Z., Zhang X., Yin S., Ye J. Cigarette smoke extract increases mitochondrial membrane permeability through activation of adenine nucleotide translocator (ANT) in lung epithelial cells. Biochem. Biophys. Res. Commun. 2020; 525(3):32143825. https://doi.org/10.1016/j.bbrc.2020.02.160

51. [Bronchial asthma. Clinical recommendations]. Moscow; 2021 (in Russian). Available at: https://spulmo.ru/upload/rekomendacyi_bronh_astma_21_23.pdf

52. Li M., Shang Y-X. Ultrastructural Changes in Rat Airway Epithelium in Asthmatic Airway Remodeling. Pathol. Res. Pract. 2014; 210(12):1038–1042. https://doi.org/10.1016/j.prp.2014.03.010

53. Mabalirajan U., Dinda A.K., Kumar S., Roshan R., Gupta P., Sharma S.K., Ghosh B. Mitochondrial structural changes and dysfunction are associated with experimental allergic asthma. J. Immunol. 2008; 181(5):3540–3548. https://doi.org/10.4049/jimmunol.181.5.3540

54. Hough K.P., Trevor J.L., Strenkowski J.G., Wang Y., Chacko B.K., Tousif S., Chanda D., Steele C., Antony V.B., Dokland T., Ouyang X., Zhang J., Duncan S.R., Thannickal V.J., Darley-Usmar V.M., Deshane J.S. Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells. Redox Biol. 2018; 18:54–64. https://doi.org/10.1016/j.redox.2018.06.009

55. Ederlé C., Charles A.L., Khayath N., Poirot A., Meyer A., Clere-Jehl R., Andres E., De Blay F., Geny B. Mitochondrial Function in Peripheral Blood Mononuclear Cells (PBMC) Is Enhanced, Together with Increased Reactive Oxygen Species, in Severe Asthmatic Patients in Exacerbation. J. Clin. Med. 2019; 8(10):1613. https://doi.org/10.3390/jcm8101613

56. Liu H., Tao S., Ma H., Jin J., Jing J., Yao L., Ma X., Li F. Functional changes of airway epithelial cells and mitochondria in rat models of asthenic lung and phlegm blocking combined with cough variant asthma. Exp. Ther. Med. 2018; 16(6):5021–5024. https://doi.org/10.3892/etm.2018.6863

57. Ramakrishnan R.K., Bajbouj K., Hachim M.Y., Mogas A.K., Mahboub B., Olivenstein R., Hamoudi R., Halwani R., Hamid Q. Enhanced mitophagy in bronchial fibroblasts from severe asthmatic patients. PLoS One 2020; 15(11):e0242695. https://doi.org/10.1371/journal.pone.0242695

58. [Chronic bronchitis. Clinical recommendations]. Moscow; 2021 (in Russian). Available at: http://www.consultant.ru/document/cons_doc_LAW_393821/