Serbest Mitokondriyal DNA’nın Sistemik Dolaşımdaki Rolü ve Hastalıkların Patogenezine Etkisi

Ayşe Tülay Aydınoğlu; Evrim Aksu Mengeş; Burcu Balcı Hayta

EN TR

Serbest Mitokondriyal DNA’nın Sistemik Dolaşımdaki Rolü ve Hastalıkların Patogenezine Etkisi

Öz

Mitokondri, oksidatif fosforilasyon ile ATP üretiminin yanı sıra üstlendiği görevler ile hücre canlılığının sürdürülebilmesinde merkezi öneme sahip çok işlevli bir organeldir. Organelin hücre canlılığına katkıda bulunmasında rol oynayan en temel özelliklerinden biri de kendine özgül genetik sistemidir. Mitokondriyal DNA mtDNA ’nın normal fizyolojik koşullarda organelin matriks kısmında bulunduğu, fakat gerek organel gerekse hücre hasarı olduğu durumda hücre dışı matrise salınarak serbest dolaşıma katıldığı belirtilmiştir. Özellikle son yıllarda mtDNA’ya ilişkin yapılan çalışmalar, organel genomunun dolaşımda üstlendiği roller ve hastalıklarla ilişkisi üzerine yoğunlaşmıştır. Sistemik dolaşımda serbest halde bulunan mtDNA’lar [circulating cell free mtDNA ccf-mtDNA ] bağışıklık sisteminde görevli Kalıp Tanıma Reseptörleri [Pattern Recognition Receptors PRRs ] tarafından Hasarla İlişkili Moleküler Yapılar [Damage Associated Molecular Patterns DAMPs ] olarak algılanarak pro-inflamatuar yanıt oluşumunda temel bir rol üstlenmektedir. Bu derlemede, ccf-mtDNA’nın sistemik dolaşıma katılma mekanizmaları ve etkileşimde bulunduğu yolakların detayına inilerek, bağışıklık sisteminin bir uyaranı olarak görev almasına ve hastalıklarla ilişkisine dair bilgiler özetlenmiştir

Anahtar Kelimeler

ccf-mtDNA,sistemik dolaşım,inflamasyon

References

1. Ernster L, Schatz G. Mitochondria: A Historical Review. J Cell Biol. 1981;91:227-55. [CrossRef]
2. West AP, Shadel GS, Ghosh S. Mitochondria in Innate Immune Responses. Nat Rev Immunol 2011;11:389-492. [CrossRef]
3. Anzell AR, Maizy R, Przyklenk K, Sanderson TH. Mitochondrial Quality Control and Disease: Insights into Ischemia-Reperfusion Injury. Mol Neurobiol 2018;55:2547-64. [CrossRef]
4. Aksu E. Megakoniyal Konjenital Müsküler Distrofi Hastalığında Mitokondri Dinamiğinin İncelenmesi. (Yayınlanmamış tez) Hacettepe Üniversitesi, Ankara, 2017. http://www.openaccess.hacettepe. edu.tr:8080/xmlui/bitstream/handle/11655/3727/10156756. pdf?sequence=3&isAllowed=y
5. Pieczenik SR ve Neustadt J. Mitochondrial Dysfunction and Molecular Pathways of Disease. Exp Mol Pathol 2007;83:84-92. [CrossRef]
6. Weinberg SE, Sena LA, Chandel NS. Mitochondria in Regulation of Innate and Adaptive Immunity. Immunity 2015;17:406-17. [CrossRef]
7. West AP, Shadel GS. Mitochondrial DNA in Innate Immune Responses and Inflammatory Pathology. Nat Rev Immunol 2017;17:363-75. [CrossRef]
8. Luft R. The Development of Mitochondrial Medicine. Proc Natl Acad Sci USA 1994;91:8731-8. [CrossRef]

9. Endo T ve Yamano K. Multiple Pathways for Mitochondrial Protein Traffic. Biol Chem 2009;390:8:723-30. [CrossRef]
10. Cole LW. The Evolution of Per-cell Organelle Number. Front. Cell Dev. Biol. 2016;4:85. [CrossRef]
11. Wiesner RJ, Ruegg JC, Morano I. Counting Target Molecules by Exponential Polymerase Chain Reaction: Copy Number of Mitochondrial DNA in Rat Tissues. Biochem Biophys Res Commun 1992;183:553-9. [CrossRef]
12. Bonawitz ND, Clayton DA, Shadel GS. Initiation and beyond: Multiple Functions of the Human Mitochondrial Transcription Machinery. Molecular Cell. 2006;24:813-25. [CrossRef]
13. 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. [CrossRef]
14. O’Rourke TW, Doudican NA, Mackereth MD, Doetsch PW, Shadel GS. Mitochondrial Dysfunction Due to Oxidative Mitochondrial DNA Damage is Reduced Through Cooperative Actions of Diverse Proteins. Mol. Cell. Biol. 2002;22:4086-93. [CrossRef]
15. Kang D ve Hamasaki N. Alterations of Mitochondrial DNA in Common Diseases and Disease States: Aging, Neurodegeneration, Heart Failure, Diabetes and Cancer. Curr Med Chem 2005;4:429-41. [CrossRef]
16. Singer TP ve Ramsay RR. Mechanism of the Neurotoxicity of MPTP. An Update. FEBS Lett.1990;274:1-8. [CrossRef]
17. Bandy B ve Davison AJ. Mitochondrial Mutations May Increase Oxidative Stress: Implications for Carcinogenesis and Aging? Free Radical. Biol. Med. 1990;8:523-39. [CrossRef]
18. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, et al. A Tolllike Receptor Recognizes Bacterial DNA. Nature 2000;408:740-45. [CrossRef]
19. Barbalat R, Ewald SE, Mouchess ML, Barton GM. Nucleic Acid Recognition by the Innate Immune System. Annu Rev Immunol 2011;29:185-214. [CrossRef]
20. Hong EE, Okitsu CY, Smith AD, Hsieh CL. Regionally Specific and Genome-Wide Analyses Conclusively Demonstrate the Absence of CpG methylation in Human Mitochondrial DNA. Mol. Cell. Biol 2013;33:2683-90. [CrossRef]
21. Bellizzi D, D’Aquila P, Scafone T, Giardano M, Riso V, Riccio A, et al. The Control Region of Mitochondrial DNA Shows an Unusual CpG and Non-CpG Methylation Pattern. DNA Research. An International Journal for Rapid Publication of Reports on Genes and Genomes. 2013;20:537-47. [CrossRef]
22. Liu B, Du Q, Chen L, Fu G, Li S, Fu L, et al. CpG Methylation Patterns of Human Mitochondrial DNA. Sci Rep 2016;6:23421. [CrossRef]
23. Jiang WW. Increased Mitochondrial DNA Content in Saliva Associated with Head and Neck Cancer. Clini Cancer Res, 2005;11:2486-91. [CrossRef]
24. Ho PWL, Pang WF, Luk CCW, Ng JKC, Chow KM, Kwan BCH, et al. Urinary Mitochondrial DNA Level as a Biomarker of Acute Kidney Injury Severity. Kidney Dis 2017;3:78-83 [CrossRef]
25. Hajizadeh S, DeGroot J, TeKoppele JM, Tarkowski A, Collins LV. Extracellular Mitochondrial DNA and Oxidatively Damaged DNA in Synovial Fluid of Patients with Rheumatoid Arthritis. Arthritis Res Ther 2003;5:R234-40. [CrossRef]
26. Pyle A, Anugrha H, Kurzawa-Akanbi M, Yarnall A, Burn D, Hudson G. Reduced Mitochondrial DNA Copy Number is a Biomarker of Parkinson’s Disease. Neurobiol Aging 2016;38:216.e7-216.e10. [CrossRef]
27. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W et al. Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury. Nature 2010;464:104-7. [CrossRef]
28. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC et al. Autophagy Proteins Regulate Innate Immune Responses by Inhibiting the Release of Mitochondrial DNA Mediated by the NALP3 Inflammasome. Nat. Immunol 2011;12:222-30 [CrossRef]
29. Riley JS, Quarato G, Cloix C, Lopez J, O’Prey J, Pearson M et al. Mitochondrial Inner Membrane Permeabilization Enables mtDNA Release During Apoptosis. EMBO J. 2018;37:e99298 [CrossRef]
30. Thurairajah K, Briggs GD, Balogh ZJ. The Source of Cell-free Mitochondrial DNA in Trauma and Potential Therapeutic Strategies. Eur J Trauma Emerg Surg 2018;44:325-34. [CrossRef]
31. Lichtenstein AV, Melkonyan HS, Tomeı LD, Umansky SR. Circulating Nucleic Acids and Apoptosis. Ann NY Acad Sci. 2006;945:239-49. [CrossRef]
32. Chiu RW, Chan LY, Lam NY, Tsui NB, Ng EK, Rainer TH, et al. Quantitative Analysis of Circulating Mitochondrial DNA in Plasma. Clin Chem 2003;49:719-26. [CrossRef]
33. Chandrananda D, Thorne NP, Bahlo M. High-Resolution Characterization of Sequence Signatures Due to Non-random Cleavage of Cell-free DNA. BMC Med Genomics 2015;8:29. [CrossRef]
34. Wilkins HM, Weidling IW, Ji Y, Swerdlow RH. Mitochondriaderived Damage-Associated Molecular Patterns in Neurodegeneration. Front Immunol. 2017;8:508. [CrossRef]
35. Caielli S, Athale S, Domic B, Murat E, Chandra M, Banchereau R, et al. Oxidized Mitochondrial Nucleoids Released by Neutrophils Drive Type I Interferon Production in Human Lupus. J Exp Med 2016;213:697-713. [CrossRef]
36. García N, García JJ, Correa F, Chávez E. The Permeability Transition Pore as a Pathway for the Release of Mitochondrial DNA. Life Sci. 2005;76:2873-80. [CrossRef]
37. García N ve Chávez E. Mitochondrial DNA Fragments Released Through the Permeability Transition Pore Correspond to Specific Gene Size. Life Sci. 2007;81:1160-6. [CrossRef]
38. Patrushev M, Kasymov V, Patrusheva V, Ushakova T, Gogvadze V, Gaziev A. Mitochondrial Permeability Transition Triggers the Release of mtDNA Fragments. Cell. Mol. Life Sci. 2004;61:3100-3 [CrossRef ]
39. Gyorgy B, Szabo TG, Pasztoi M, Pal Z, Misjak P, Aradi B, et al. Membrane Vesicles, Current State-of-the-Art: Emerging Role of Extracellular Vesicles. Cell Mol Life Sci 2011;68:2667-88. [CrossRef]
40. Picca A, Lezza AMS, Leeuwenburgh C, Pesce V, Calvani R, Landi F, et al. Fueling Inflamm-Aging Through Mitochondrial Dysfunction: Mechanisms and Molecular Targets. Int J Mol Sci 2017;18:pii:E933. [CrossRef]
41. Nakahira K, Hisata S, Choi AMK. The Roles of Mitochondrial DamageAssociated Molecular Patterns in Diseases. Antioxid Redox Signal 2015;23:1329-50. [CrossRef]
42. Chunju F, Xiawei W, Yuquan W. Mitochondrial DNA in the Regulation of Innate Immune Responses. Protein Cell 2016;7:11- 6. [CrossRef ]
43. Wei X, Shao B, He Z, Ye T, Luo M, Sang Y, et al. Cationic Nanocarriers Induce Cell Necrosis Through Impairment of Na+/K+-ATPase and Cause Subsequent Inflammatory Response. Cell Res. 2015;25:237- 53. [CrossRef]
44. Julian MW, Shao G, VanGundy ZC, Papenfuss TL, Crouser ED. Mitochondrial Transcription Factor A, an Endogenous Danger Signal, Promotes TNFα Release via RAGE- and TLR9- Responsive Plasmacytoid Dendritic Cells. PLoS One 2013;8:e72354. [CrossRef ]
45. Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, et al. Oxidized Mitochondrial DNA Activates the NLRP3 Inflammasome During Apoptosis. Immunity 2012;36:401-14. [CrossRef]
46. Boyapati RK, Tamborska A, Doward DA, Ho GT. Advances in the Understanding of Mitochondrial DNA as a Pathogenic Factor in Inflammatory Diseases. F1000Res. 2017;6:169. [CrossRef]
47. West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, et al. Mitochondrial DNA Stress Primes the Antiviral Innate Immune Response. Nature 2015; 520:553-7. [CrossRef]
48. Gao D, Wu J, Wu YT, Du F, Aroh C, Yan N, et al. Cyclic GMP–AMP Synthase is an Innate Immune Sensor of HIV and Other Retroviruses. Science 2013:341;903-6. [CrossRef]
49. Rongvaux A, Willinger T, Martinek J, Strowing T, Gearty SV, Teichmann LL, et al. Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA. Cell 2014;159:1563-77. [CrossRef]
50. White MJ, McArthur K, Metcalf D, Lane RM, Cambier JC, Herold MJ, et al. Apoptotic Caspases Suppress mtDNA-induced STING-Mediated Type I IFN Production. Cell 2014;159:1549-62. [CrossRef]
51. Wang H, Li T, Chen S, Gu Y, Ye S. Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and A ProofofConcept Trial of Metformin. Arthritis Rheumatol 2015;67:3190-200. [CrossRef]
52. Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, et al. Neutrophil Extracellular Traps Enriched in Oxidized Mitochondrial DNA are Interferogenic and Contribute to Lupus-like Disease. Nat. Med 2016;22:146-53. [CrossRef]
53. McIlroy DJ, Jarnicki AG, Au GG, Lott N, Smith DW, Hansbro PM, et al. Mitochondrial DNA Neutrophil Extracellular Traps are Formed After Trauma and Subsequent Surgery. J. Crit Care 2014;29:1133.e1-5. [CrossRef]
54. Zhang B, Asadi S, Weng Z, Sismanopoulos N, Theoharides TC. Stimulated Human Mast Cells Secrete Mitochondrial Components That Have Autocrine and Paracrine Inflammatory Actions. PLoS One 2012;7:12,e49767. [CrossRef]
55. Boudreau LH, Duchez AC, Cloutier N, Soulet D, Martin N, Bollinger J, et al. Platelets Release Mitochondria Serving as Substrate for Bactericidal Group IIA-Secreted Phospholipase A2 to Promote Inflammation. Blood 2014;124: 2173-83. [CrossRef]
56. Diaz LA JR, Bardelli A. Liquid biopsies: Genotyping Circulating Tumor DNA. J Clin Oncol. 2014; 32:579-86. [CrossRef]
57. Elshimali YI, Khaddour H, Sarkissyan M, Wu Y, Vadgama JV. The Clinical Utilization of Circulating Cell Free DNA (CCFDNA) in Blood of Cancer Patients. Int J Mol Sci, 2013;14:18925-58. [CrossRef]

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Turkish

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Ayşe Tülay Aydınoğlu

Evrim Aksu Mengeş

Burcu Balcı Hayta

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September 1, 2020

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Year 2020 Number: 3

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https://izlik.org/JA54ZB23RK

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Aydınoğlu AT, Mengeş EA, Hayta BB (September 1, 2020) Serbest Mitokondriyal DNA’nın Sistemik Dolaşımdaki Rolü ve Hastalıkların Patogenezine Etkisi. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 3 372–379.

Serbest Mitokondriyal DNA’nın Sistemik Dolaşımdaki Rolü ve Hastalıkların Patogenezine Etkisi

The Role of Circulating Cell-Free Mitochondrial Dna In Systemic Circulation and Its Effect On Diseases Pathogenesis

Abstract

Keywords

Serbest Mitokondriyal DNA’nın Sistemik Dolaşımdaki Rolü ve Hastalıkların Patogenezine Etkisi

Öz

Anahtar Kelimeler

References

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