CLINICAL CYTOLOGY OF THE LIVER: MITOCHONDRIA
Keywords:
liver, mitochondria, fixation, changes, visualization
Abstract
Background. In recent years, ideas about mitochondria (MX) previously considered only as «energy blocks» of the cell that produce ATP have changed. MX is one of the targets of the HCV attack in chronic hepatitis C (CHC). The objective of the study is to present the morphological characteristic of liver MX in chronic hepatitis C using the original method of tissue fixation. Materials and methods. We employed methods of light microscopy of semi-thin sections with the use of improved methods of fixation and electron microscopy of ultrathin sections. To take pictures, a complex comprising a digital camera and the image processing program Olympus Mega View III (Germany) were used. Results. As a result of the research, the following variants of changes in hepatocyte MX were identified: swelling, condensation (compaction) of the matrix, disruption of the crista structure; disruption of mitochondrial fusion; mitochondrial division and fragmentation; destruction of MX by the formation of mitophagolysosome. The illustrations of macroautophagy, in which the degradation of large cell organelles and large protein aggregates with the formation of autophagosome occurs, are given. The initiating links of the mitochondrial apoptosis pathway have been studied in HIV-infected patients with chronic hepatitis C who are on antiretroviral therapy. Conclusion. The visualization of MX in liver biopsy, their distribution in the hepatocyte cytoplasm, the number, variability and monitoring of changes are important criteria for assessing the functional state of the liver under viral damage. The osmium fixative has obvious advantages over other existing reagents.References
1. Scheffler IE. Mitochondria. New York: Wiley-Liss; 1999. 480 р.
2. Yoshimitsu K, Hiromi N. Intra-and Intercellular Quality Control Mechanisms of Mitochondria. Cells. 2017;7(1):1. doi: 10.3390/cells7010001.
3. Nelson N, Schatz G. Energy-dependent processing of cytoplasmically made precursors to mitochondrial proteins. Proc. Natl. Asad. Sci. USA. 1979;76(9):4365-4369.
4. Van der Bliek AM, Sedensky MM, Morgan PG. Cell Biology of the Mitochondrion. Genetics. 2017;207(3):843-871. doi: 10.1534/genetics.117.300262.
5. Vakifahmetoglu-Norberg H, Ouchida AT, Norberg E. The role of mitochondria in metabolism and cell death. Biochem. Biophys. Res. Commun. 2017;482:426-431. doi: 10.1016/j.bbrc.2016.11.088.
6. Kiriyma Y, Nochi H. Intra- and Intercellular Quality Control Mechanisms of Mitochondria. Cells. 2018;7(1):1. 7. Lyu BN, Lyu MB, Ismailov BI. Rol mitohondrij v razvitii i regulyacii urovnya okislitelnogo stressa v norme, pri kletochnyh patologiyah i reversii opuholevyh kletok. Advances in Modern Biology. 2006;126(4):388-398. (Russian).
8. Yoshimitsu K, Hiromi N. The Function of Autophagy in Neurodegenerative Diseases. Int. J. Mol. Sci. 2015;16(11):26797-26812.
9. Pan D, Lindau C, Lagies S, Wiedemann N, Kammerer B. Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses. Metabolomics. 2018;14(5):59. doi: 10.1007/s11306-018-1352-x.
10. Kim SJ, Syed GH, Khan M, Chiu WW, Sohail MA, Gish RG, Siddigui A. Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence. Proc. Natl. Acad. Sci. USA. 2014;111(17):6413-6418. doi: 10.1073/pnas.1321114111.
11. Chan DC. Mitochondria: Dynamic organelles in disease, aging, and development. Cell. 006;125:1241-1252. doi: 10.1016/j.cell.2006.06.010.
12. Kurbat MN, Tsyrkunov VM, Kondratovich IA. Gepatotoksichnost startovoj skhemy antiretrovirusnoj terapii VICh-infekcii. Medicinskaja panorama [Medical panorama]. 2015;1:3-6. (Russian).
13. Piccoli C, Scrima R, Quarato G, D’Aprile A, Ripoli M, Lecce L, Boffoli D, Moradpour D, Capitanio N. Hepatitis C virus protein expression causes calcium-mediated mitochondrial bioenergetic dysfunction and nitro-oxidative stress. Hepatology. 2007;46:58-65. doi: 10.1002/hep.21679.
14. Quarato G, Scrima R, Agriesti F, Moradpour D, Capitanio N, Piccoli C. Targeting mitochondria in the infection strategy of the hepatitis C virus. Int. J. Biochem. Cell Biol. 2013;45:156-166. doi: 10.1016/j.biocel.2012.06.008.
15. Wang T, Weinman SA. Interactions between Hepatitis C Virus and Mitochondria: Impact on Pathogenesis and Innate Immunity. Curr. Pathobiol. Rep. 2013;1(3):179-187.
16. Sato T, Takagi I. An electron microscopic study of specimen-fixed for longer periods in phosphate buffered formalin. Journal of Electron Microscopy. 1982;31(4):423-428. doi: 10.1093/oxfordjournals.jmicro.a050388.
17. Andreev VP, Matievskaya NV, Tsyrkunov VM, Khombak VV, inventors. Method for fixing liver biopsy specimens. BY рatent 20209. 2016 Ijun 30. (Russian).
18. Glauert RH. Araldite as embedding medium for electron microscopy. Journal of Biophysical and Biochemical Cytology. 1958;4:409-414.
19. Millonig GA. Advantages of a phosphate buffer for osmium tetroxide solutions in fixation. Journal of Applied Physics. 1961;32:1637-1643.
20. Watson ML. Staining of tissue sections for electron microscopy with heavy metals. Journal of Biophysical and Biochemical Cytology. 1958;4:475-478.
21. Glauert AM, editor. Practical Methods in Electron Microscopy. Vol. 3, pt. 1, Glauert AM. Fixation, degydratation and embedding of biological specimens. New York: American Elsevier; 1975. 207 p.
22. Reynolds ES. The use of lead citrate at high pH as an electronopaque stain in electron microscopy. J. Cell Biol. 1963;17(1):208-212.
23. Schaff Z, Lapis K, Andre J. Study of the tridimensional structure of intramitochondrial crystalline inclusions. J. Microscopie. 1974;20:259-264.
24. Serov VV, Lapish K, Sekamova S, Beketova TP; USSR Academy of Medical Sciences. Morfologicheskaja diagnostika zabolevanij pecheni [Morphological diagnosis of liver diseases]. Moscow: Meditsina; 1989. 336 p. (Russian).
25. Riede U, Sandritter W, Mittermayer С. Circulatory shock: a review. Pathology. 1981;13(2):299-311.
26. Ripoli M, D’Aprile A, Quarato G, Sarasin-Filipowicz M,Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C. Hepatitis C Viruslinked mitochondrial dysfunction promotes hypoxia-inducible factor 1 alpha-mediated glycolytic adaptation. J. Virol. 2010;84(1):647-660. doi: 10.1128/JVI.00769-09.
27. Siavoshian S, Abraham JD, Thumann C, Kieny MP, Schuster C. Hepatitis C Virus Core, NS3, NS5A, NS5B Proteins Induce Apoptosis in Mature Dendritic Cells. J. Med. Virol. 2005;75(3):402-411. doi: 10.1002/jmv.20283.
28. Brault C, Levy PL, Bartosch B. Hepatitis C virus-induced mitochondrial dysfunctions. Viruses. 2013;5(3):954-980. doi: 10.3390/v5030954.
29. Ding WX, Li M, Biazik JM, Morgan DG, Guo F, Ni HM, Goheen M, Eskelinen EL, Yin XM. Electron microscopic analysis of a spherical mitochondrial structure. J. Biol. Chem. 2012;287(50):42373-42378. doi: 10.1074/jbc.M112.413674.
30. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat. Rev. Mol. Cell Biol. 2010;11(12):872-884. doi: 10.1038/nrm3013.
31. Chan DC. Mitochondria: dynamic organelles in disease, aging, and development. Cell. 2006;125(7):1241-1252. doi: 10.1016/j.cell.2006.06.010.
32. Fujioka H, Tandler B, Hoppel CL. Mitochondrial division in rat cardiomyocytes: an electron microscope study. Anat. Rec. (Hoboken). 2012;295(9):1455-1461. doi: 10.1002/ar.22523.
33. Fujioka H, Tandler B, Consolo MC, Karnik P. Division of Mitochondria in Cultured Human Fibroblasts. Microsc. Res. Tech. 2013;76(12):1213-1216. doi: 10.1002/jemt.22287.
34. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012;393(7):547-564. doi: 10.1515/hsz-2012-0119.
35. Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011;146(5):682-695. doi.org/10.1016/j.cell.2011.07.030.
36. Polla BS, Banzet N, Dall AJ, Patrick AA. Vignola M. Les mitochondries, Carrefour entre vie et mort cellulaire : rôles des protéines de stress et consequences sur l’inflammation. Med. Sci.1998;14(1):18-25. (French).
37. Benali-Furet NL, Chami M, Houel L, De Giorgi F, Vernejoul F, Lagorce D, Buscail L, Bartenschlager R, Ichas F, Rizzuto R, Paterlini-Bréchot P. Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion. Oncogene. 2005;24(31):4921-4933. doi: 10.1038/sj.onc.1208673.
38. Giacomello M, Pellegrini L. The coming of age of the mitochondria–ER contact: a matter of thickness. Cell Death Differ. 2016;23(9):1417-1427. doi: 10.1038/cdd.2016.52.
39. Pupyshev AB. Reparativnaja autofagija i autofagovaja gibel kletki. Funkcionalnye i reguljatornye aspekty [Reparative autophagy and autophagy death of cells. Functional and regulatory aspects]. Tsitologiya [Cytology]. 2014;56(3):179-189. (Russian).
40. Kurbat MN, Tsyrkunov VM. Vzaimosvjaz mezhdu proapoptoticheskimi faktorami mitohondrialnogo zvena apoptoza pri lekarstvennom gepatite. In: Zharko VI, editor. Dostizhenija medicinskoj nauki Belarusi: recenziruemyj nauchno-prakticheskij ezhegodnik [Accomplishments of Medical Science in Belarus]. Minsk: GU RNMB; 2016. [Internet]. Available from: http://med.by/dmn/book. php?book=16-5_4. (Russian).
41. Ivashkin VT. Mekhanizmy immunnoj tolerantnosti i patologii pecheni. Rossijskij Zhurnal Gastrojenterologii, Gepatologii, Koloproktologii [The Russian Journal of Gastroenterology, Hepatology, Coloproctology]. 2009;19(2):2-13. (Russian).
42. Crow, MT. Hypoxia, BNip3 proteins, and the mitochondrial death pathway in cardiomyocytes. Circ. Res. 2002;91(3):183-185.
43. Moyle G. Mitochondrial toxicity: myths and facts. J. HIV Ther. 2004;9(2):45-47.
2. Yoshimitsu K, Hiromi N. Intra-and Intercellular Quality Control Mechanisms of Mitochondria. Cells. 2017;7(1):1. doi: 10.3390/cells7010001.
3. Nelson N, Schatz G. Energy-dependent processing of cytoplasmically made precursors to mitochondrial proteins. Proc. Natl. Asad. Sci. USA. 1979;76(9):4365-4369.
4. Van der Bliek AM, Sedensky MM, Morgan PG. Cell Biology of the Mitochondrion. Genetics. 2017;207(3):843-871. doi: 10.1534/genetics.117.300262.
5. Vakifahmetoglu-Norberg H, Ouchida AT, Norberg E. The role of mitochondria in metabolism and cell death. Biochem. Biophys. Res. Commun. 2017;482:426-431. doi: 10.1016/j.bbrc.2016.11.088.
6. Kiriyma Y, Nochi H. Intra- and Intercellular Quality Control Mechanisms of Mitochondria. Cells. 2018;7(1):1. 7. Lyu BN, Lyu MB, Ismailov BI. Rol mitohondrij v razvitii i regulyacii urovnya okislitelnogo stressa v norme, pri kletochnyh patologiyah i reversii opuholevyh kletok. Advances in Modern Biology. 2006;126(4):388-398. (Russian).
8. Yoshimitsu K, Hiromi N. The Function of Autophagy in Neurodegenerative Diseases. Int. J. Mol. Sci. 2015;16(11):26797-26812.
9. Pan D, Lindau C, Lagies S, Wiedemann N, Kammerer B. Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses. Metabolomics. 2018;14(5):59. doi: 10.1007/s11306-018-1352-x.
10. Kim SJ, Syed GH, Khan M, Chiu WW, Sohail MA, Gish RG, Siddigui A. Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence. Proc. Natl. Acad. Sci. USA. 2014;111(17):6413-6418. doi: 10.1073/pnas.1321114111.
11. Chan DC. Mitochondria: Dynamic organelles in disease, aging, and development. Cell. 006;125:1241-1252. doi: 10.1016/j.cell.2006.06.010.
12. Kurbat MN, Tsyrkunov VM, Kondratovich IA. Gepatotoksichnost startovoj skhemy antiretrovirusnoj terapii VICh-infekcii. Medicinskaja panorama [Medical panorama]. 2015;1:3-6. (Russian).
13. Piccoli C, Scrima R, Quarato G, D’Aprile A, Ripoli M, Lecce L, Boffoli D, Moradpour D, Capitanio N. Hepatitis C virus protein expression causes calcium-mediated mitochondrial bioenergetic dysfunction and nitro-oxidative stress. Hepatology. 2007;46:58-65. doi: 10.1002/hep.21679.
14. Quarato G, Scrima R, Agriesti F, Moradpour D, Capitanio N, Piccoli C. Targeting mitochondria in the infection strategy of the hepatitis C virus. Int. J. Biochem. Cell Biol. 2013;45:156-166. doi: 10.1016/j.biocel.2012.06.008.
15. Wang T, Weinman SA. Interactions between Hepatitis C Virus and Mitochondria: Impact on Pathogenesis and Innate Immunity. Curr. Pathobiol. Rep. 2013;1(3):179-187.
16. Sato T, Takagi I. An electron microscopic study of specimen-fixed for longer periods in phosphate buffered formalin. Journal of Electron Microscopy. 1982;31(4):423-428. doi: 10.1093/oxfordjournals.jmicro.a050388.
17. Andreev VP, Matievskaya NV, Tsyrkunov VM, Khombak VV, inventors. Method for fixing liver biopsy specimens. BY рatent 20209. 2016 Ijun 30. (Russian).
18. Glauert RH. Araldite as embedding medium for electron microscopy. Journal of Biophysical and Biochemical Cytology. 1958;4:409-414.
19. Millonig GA. Advantages of a phosphate buffer for osmium tetroxide solutions in fixation. Journal of Applied Physics. 1961;32:1637-1643.
20. Watson ML. Staining of tissue sections for electron microscopy with heavy metals. Journal of Biophysical and Biochemical Cytology. 1958;4:475-478.
21. Glauert AM, editor. Practical Methods in Electron Microscopy. Vol. 3, pt. 1, Glauert AM. Fixation, degydratation and embedding of biological specimens. New York: American Elsevier; 1975. 207 p.
22. Reynolds ES. The use of lead citrate at high pH as an electronopaque stain in electron microscopy. J. Cell Biol. 1963;17(1):208-212.
23. Schaff Z, Lapis K, Andre J. Study of the tridimensional structure of intramitochondrial crystalline inclusions. J. Microscopie. 1974;20:259-264.
24. Serov VV, Lapish K, Sekamova S, Beketova TP; USSR Academy of Medical Sciences. Morfologicheskaja diagnostika zabolevanij pecheni [Morphological diagnosis of liver diseases]. Moscow: Meditsina; 1989. 336 p. (Russian).
25. Riede U, Sandritter W, Mittermayer С. Circulatory shock: a review. Pathology. 1981;13(2):299-311.
26. Ripoli M, D’Aprile A, Quarato G, Sarasin-Filipowicz M,Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C. Hepatitis C Viruslinked mitochondrial dysfunction promotes hypoxia-inducible factor 1 alpha-mediated glycolytic adaptation. J. Virol. 2010;84(1):647-660. doi: 10.1128/JVI.00769-09.
27. Siavoshian S, Abraham JD, Thumann C, Kieny MP, Schuster C. Hepatitis C Virus Core, NS3, NS5A, NS5B Proteins Induce Apoptosis in Mature Dendritic Cells. J. Med. Virol. 2005;75(3):402-411. doi: 10.1002/jmv.20283.
28. Brault C, Levy PL, Bartosch B. Hepatitis C virus-induced mitochondrial dysfunctions. Viruses. 2013;5(3):954-980. doi: 10.3390/v5030954.
29. Ding WX, Li M, Biazik JM, Morgan DG, Guo F, Ni HM, Goheen M, Eskelinen EL, Yin XM. Electron microscopic analysis of a spherical mitochondrial structure. J. Biol. Chem. 2012;287(50):42373-42378. doi: 10.1074/jbc.M112.413674.
30. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat. Rev. Mol. Cell Biol. 2010;11(12):872-884. doi: 10.1038/nrm3013.
31. Chan DC. Mitochondria: dynamic organelles in disease, aging, and development. Cell. 2006;125(7):1241-1252. doi: 10.1016/j.cell.2006.06.010.
32. Fujioka H, Tandler B, Hoppel CL. Mitochondrial division in rat cardiomyocytes: an electron microscope study. Anat. Rec. (Hoboken). 2012;295(9):1455-1461. doi: 10.1002/ar.22523.
33. Fujioka H, Tandler B, Consolo MC, Karnik P. Division of Mitochondria in Cultured Human Fibroblasts. Microsc. Res. Tech. 2013;76(12):1213-1216. doi: 10.1002/jemt.22287.
34. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012;393(7):547-564. doi: 10.1515/hsz-2012-0119.
35. Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011;146(5):682-695. doi.org/10.1016/j.cell.2011.07.030.
36. Polla BS, Banzet N, Dall AJ, Patrick AA. Vignola M. Les mitochondries, Carrefour entre vie et mort cellulaire : rôles des protéines de stress et consequences sur l’inflammation. Med. Sci.1998;14(1):18-25. (French).
37. Benali-Furet NL, Chami M, Houel L, De Giorgi F, Vernejoul F, Lagorce D, Buscail L, Bartenschlager R, Ichas F, Rizzuto R, Paterlini-Bréchot P. Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion. Oncogene. 2005;24(31):4921-4933. doi: 10.1038/sj.onc.1208673.
38. Giacomello M, Pellegrini L. The coming of age of the mitochondria–ER contact: a matter of thickness. Cell Death Differ. 2016;23(9):1417-1427. doi: 10.1038/cdd.2016.52.
39. Pupyshev AB. Reparativnaja autofagija i autofagovaja gibel kletki. Funkcionalnye i reguljatornye aspekty [Reparative autophagy and autophagy death of cells. Functional and regulatory aspects]. Tsitologiya [Cytology]. 2014;56(3):179-189. (Russian).
40. Kurbat MN, Tsyrkunov VM. Vzaimosvjaz mezhdu proapoptoticheskimi faktorami mitohondrialnogo zvena apoptoza pri lekarstvennom gepatite. In: Zharko VI, editor. Dostizhenija medicinskoj nauki Belarusi: recenziruemyj nauchno-prakticheskij ezhegodnik [Accomplishments of Medical Science in Belarus]. Minsk: GU RNMB; 2016. [Internet]. Available from: http://med.by/dmn/book. php?book=16-5_4. (Russian).
41. Ivashkin VT. Mekhanizmy immunnoj tolerantnosti i patologii pecheni. Rossijskij Zhurnal Gastrojenterologii, Gepatologii, Koloproktologii [The Russian Journal of Gastroenterology, Hepatology, Coloproctology]. 2009;19(2):2-13. (Russian).
42. Crow, MT. Hypoxia, BNip3 proteins, and the mitochondrial death pathway in cardiomyocytes. Circ. Res. 2002;91(3):183-185.
43. Moyle G. Mitochondrial toxicity: myths and facts. J. HIV Ther. 2004;9(2):45-47.
Published
2019-02-19
How to Cite
1.
Andreev VP, Tsyrkunov VM, Kravchuk RI, Kurbat MN. CLINICAL CYTOLOGY OF THE LIVER: MITOCHONDRIA. journalHandG [Internet]. 2019Feb.19 [cited 2024Nov.21];2(2):143-5. Available from: http://hepatogastro.grsmu.by/index.php/journalHandG/article/view/78
Section
Оригинальные исследования
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