Research progress of mitochondrial DNA as a pathogenic factor in diseases_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

FAN Jingxiu ¹ ,  ZHU Huili ²

1. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;
2. Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

ZHU Huili, Email: 13551287548@139.com

Keywords：

Mitochondria; mitochondrial DNA; pathogenicity; review

DOI：

10.7507/1007-4848.202003016

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Mitochondrial DNA (mtDNA) is the circulating genome in mitochondria, and it is easy to accumulate oxidative damage, causing mitochondrial dysfunction, and then cell dysfunction, and even tissue and body pathological changes, leading to diseases. As a pro-inflammatory, inflammatory, and even predictive factor, mtDNA is directly involved in the inflammatory response and the pathogenesis of many diseases. This article aims to review the current pathogenesis of mtDNA damage and its pathogenic role in various human diseases.

Citation： FAN Jingxiu, ZHU Huili. Research progress of mitochondrial DNA as a pathogenic factor in diseases. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2020, 27(10): 1242-1246. doi: 10.7507/1007-4848.202003016 Copy

1.	Boyapati RK, Rossi AG, Satsangi J, <italic>et al</italic>. Gut mucosal DAMPs in IBD: From mechanisms to therapeutic implications. Mucosal Immunol, 2016, 9(3): 567-582.
2.	Li Y, Huang W, Yu Q, <italic>et al</italic>. Lower mitochondrial DNA content relates to high-altitude adaptation in Tibetans. Mitochondrial DNA A DNA Mapp Seq Anal, 2016, 27(1): 753-757.
3.	Gray K, Kumar S, Figg N, <italic>et al</italic>. Effects of DNA damage in smooth muscle cells in atherosclerosis. Circ Res, 2015, 116(5): 816-826.
4.	Orekhov AN, Poznyak AV, Sobenin IA, et al. Mitochondrion as a selective target for treatment of atherosclerosis: Role of mitochondrial DNA mutations and defective mitophagy in the pathogenesis of atherosclerosis and chronic inflammation. Curr Neuropharmacol, 2019. [Epub ahead of print].
5.	Friedman JR, Nunnari J. Mitochondrial form and function. Nature, 2014, 505(7483): 335-343.
6.	Wei X, Shao B, He Z, <italic>et al</italic>. Cationic nanocarriers induce cell necrosis through impairment of Na(+)/K(+)-ATPase and cause subsequent inflammatory response. Cell Res, 2015, 25(2): 237-253.
7.	Lin J, Jing R, Pan L. Role and mechanism of mitochondrial DNA mediated Toll-like receptor 9-myeloid differentiation factor 88 signaling pathway activation in rats with ventilator-induced lung injury. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2018, 30(1): 13-17.
8.	Zhang Y, Guallar E, Ashar FN, <italic>et al</italic>. Association between mitochondrial DNA copy number and sudden cardiac death: findings from the Atherosclerosis Risk in Communities study (ARIC). Eur Heart J, 2017, 38(46): 3443-3448.
9.	Yue P, Jing S, Liu L, <italic>et al</italic>. Association between mitochondrial DNA copy number and cardiovascular disease: Current evidence based on a systematic review and meta-analysis. PLoS One, 2018, 13(11): e0206003.
10.	Corsi S, Iodice S, Vigna L, <italic>et al</italic>. Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity. Clin Epigenetics, 2020, 12(1): 29.
11.	Hu H, Lin Y, Xu X, <italic>et al</italic>. The alterations of mitochondrial DNA in coronary heart disease. Exp Mol Pathol, 2020, 114: 104412.
12.	Liu LP, Cheng K, Ning MA, <italic>et al</italic>. Association between peripheral blood cells mitochondrial DNA content and severity of coronary heart disease. Atherosclerosis, 2017, 261: 105-110.
13.	Chen S, Xie X, Wang Y, <italic>et al</italic>. Association between leukocyte mitochondrial DNA content and risk of coronary heart disease: A case-control study. Atherosclerosis, 2014, 237(1): 220-226.
14.	Liu J, Cai X, Xie L, <italic>et al</italic>. Circulating cell free mitochondrial DNA is a biomarker in the development of coronary heart disease in the patients with type 2 diabetes. Clin Lab, 2015, 61(7): 661-667.
15.	Liu J, Zou Y, Tang Y, <italic>et al</italic>. Circulating cell-free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus. J Diabetes Investig, 2016, 7(1): 109-114.
16.	Bliksøen M, Mariero LH, Ohm IK, <italic>et al</italic>. Increased circulating mitochondrial DNA after myocardial infarction. Int J Cardiol, 2012, 158(1): 132-134.
17.	Wang L, Xie L, Zhang Q, <italic>et al</italic>. Plasma nuclear and mitochondrial DNA levels in acute myocardial infarction patients. Coron Artery Dis, 2015, 26(4): 296-300.
18.	Qin C, Gu J, Liu R, <italic>et al</italic>. Release of mitochondrial DNA correlates with peak inflammatory cytokines in patients with acute myocardial infarction. Anatol J Cardiol, 2017, 17(3): 224-228.
19.	Lubkin DT, Bishawi M, Barbas AS, <italic>et al</italic>. Extracellular mitochondrial DNA and N-formyl peptides in trauma and critical illness: A systematic review. Crit Care Med, 2018, 46(12): 2018-2028.
20.	Timmermans K, Kox M, Vaneker M, <italic>et al</italic>. Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients. Intensive Care Med, 2016, 42(4): 551-561.
21.	Prikhodko AS, Shabanov AK, Zinovkina LA, <italic>et al</italic>. Pure mitochondrial DNA does not activate human neutrophils in vitro. Biochemistry (Mosc), 2015, 80(5): 629-635.
22.	Kung CT, Hsiao SY, Tsai TC, <italic>et al</italic>. Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room. J Transl Med, 2012, 10: 130.
23.	Bhagirath VC, Dwivedi DJ, Liaw PC. Comparison of the proinflammatory and procoagulant properties of nuclear, mitochondrial, and bacterial DNA. Shock, 2015, 44(3): 265-271.
24.	Timmermans K, Kox M, Scheffer GJ, <italic>et al</italic>. Plasma nuclear and mitochondrial DNA Levels, and markers of inflammation, shock, and organ damage in patients with septic shock. Shock, 2016, 45(6): 607-612.
25.	Lu CH, Chang WN, Tsai NW, <italic>et al</italic>. The value of serial plasma nuclear and mitochondrial DNA levels in adult community-acquired bacterial meningitis. QJM, 2010, 103(3): 169-175.
26.	Garrabou G, Morén C, López S, <italic>et al</italic>. The effects of sepsis on mitochondria. J Infect Dis, 2012, 205(3): 392-400.
27.	Di Caro V, Walko TD, Bola RA, <italic>et al</italic>. Plasma mitochondrial DNA--a novel DAMP in pediatric sepsis. Shock, 2016, 45(5): 506-511.
28.	Gu X, Yao Y, Wu G, <italic>et al</italic>. The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome. PLoS One, 2013, 8(8): e72834.
29.	Jansen MPB, Pulskens WP, Butter LM, <italic>et al</italic>. Mitochondrial DNA is released in urine of SIRS patients with acute kidney injury and correlates with severity of renal dysfunction. Shock, 2018, 49(3): 301-310.
30.	Yu M. Circulating cell-free mitochondrial DNA as a novel cancer biomarker: Opportunities and challenges. Mitochondrial DNA, 2012, 23(5): 329-332.
31.	Mohamed Yusoff AA, Mohd Nasir KN, Haris K, <italic>et al</italic>. Detection of somatic mutations in the mitochondrial DNA control region D-loop in brain tumors: The first report in Malaysian patients. Oncol Lett, 2017, 14(5): 5179-5188.
32.	Mohamed Yusoff AA. Role of mitochondrial DNA mutations in brain tumors: A mini-review. J Cancer Res Ther, 2015, 11(3): 535-544.
33.	Chang X, Bakay M, Liu Y, et al. Mitochondrial DNA haplogroups and susceptibility to neuroblastoma. J Natl Cancer Inst, 2020. [Epub ahead of print].
34.	Meng S, De Vivo I, Liang L, <italic>et al</italic>. Pre-diagnostic leukocyte mitochondrial DNA copy number and risk of lung cancer. Oncotarget, 2016, 7(19): 27307-27312.
35.	Nissanka N, Moraes CT. Mitochondrial DNA heteroplasmy in disease and targeted nuclease-based therapeutic approaches. EMBO Rep, 2020: e49612.
36.	Harrington JS, Huh JW, Schenck EJ, <italic>et al</italic>. Circulating mitochondrial DNA as predictor of mortality in critically ill patients: A systematic review of clinical studies. Chest, 2019, 156(6): 1120-1136.
37.	Nakahira K, Kyung SY, Rogers AJ, <italic>et al</italic>. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med, 2013, 10(12): e1001577.
38.	Baysa A, Fedorov A, Kondratov K, <italic>et al</italic>. Release of mitochondrial and nuclear DNA during on-pump heart surgery: Kinetics and relation to extracellular vesicles. J Cardiovasc Transl Res, 2019, 12(3): 184-192.
39.	秦超毅, 古君, 钱宏, 等. 体外循环围手术期血液中线粒体 DNA 浓度变化. 中国胸心血管外科临床杂志, 2015, 22(3): 241-244.
40.	Tabata S, Yamaguchi S, Nagamine H, <italic>et al</italic>. Efficacy of FK633, an ultra-short acting glycoproteinⅡb/Ⅲa antagonist on platelet preservation during and after cardiopulmonary bypass. Eur J Cardiothorac Surg, 2004, 26(2): 289-293.
41.	Varon D, Shai E. Platelets and their microparticles as key players in pathophysiological responses. J Thromb Haemost, 2015, 13(Suppl 1): S40-S46.
42.	Boudreau LH, Duchez AC, Cloutier N, <italic>et al</italic>. Platelets release mitochondria serving as substrate for bactericidal group ⅡA-secreted phospholipase A2 to promote inflammation. Blood, 2014, 124(14): 2173-2183.
43.	Qin C, Gu J, Hu J, <italic>et al</italic>. Platelets activation is associated with elevated plasma mitochondrial DNA during cardiopulmonary bypass. J Cardiothorac Surg, 2016, 11(1): 90.
44.	Aslami H, Beurskens CJP, Tuip AM, <italic>et al</italic>. Induced hypothermia is associated with reduced circulating subunits of mitochondrial DNA in cardiac arrest patients. Mitochondrial DNA A DNA Mapp Seq Anal, 2018, 29(4): 525-528.
45.	Arnalich F, Codoceo R, López-Collazo E, <italic>et al</italic>. Circulating cell-free mitochondrial DNA: A better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation, 2012, 83(7): e162-163.
46.	Krychtiuk KA, Wurm R, Ruhittel S, <italic>et al</italic>. Release of mitochondrial DNA is associated with mortality in severe acute heart failure. Eur Heart J Acute Cardiovasc Care, 2019: 2048872618823405.
47.	Knez J, Lakota K, Božič N, <italic>et al</italic>. Correlation between mitochondrial DNA content measured in myocardium and peripheral blood of patients with non-ischemic heart failure. Genet Test Mol Biomarkers, 2017, 21(12): 736-741.

1. Boyapati RK, Rossi AG, Satsangi J, <italic>et al</italic>. Gut mucosal DAMPs in IBD: From mechanisms to therapeutic implications. Mucosal Immunol, 2016, 9(3): 567-582.
2. Li Y, Huang W, Yu Q, <italic>et al</italic>. Lower mitochondrial DNA content relates to high-altitude adaptation in Tibetans. Mitochondrial DNA A DNA Mapp Seq Anal, 2016, 27(1): 753-757.
3. Gray K, Kumar S, Figg N, <italic>et al</italic>. Effects of DNA damage in smooth muscle cells in atherosclerosis. Circ Res, 2015, 116(5): 816-826.
4. Orekhov AN, Poznyak AV, Sobenin IA, et al. Mitochondrion as a selective target for treatment of atherosclerosis: Role of mitochondrial DNA mutations and defective mitophagy in the pathogenesis of atherosclerosis and chronic inflammation. Curr Neuropharmacol, 2019. [Epub ahead of print].
5. Friedman JR, Nunnari J. Mitochondrial form and function. Nature, 2014, 505(7483): 335-343.
6. Wei X, Shao B, He Z, <italic>et al</italic>. Cationic nanocarriers induce cell necrosis through impairment of Na(+)/K(+)-ATPase and cause subsequent inflammatory response. Cell Res, 2015, 25(2): 237-253.
7. Lin J, Jing R, Pan L. Role and mechanism of mitochondrial DNA mediated Toll-like receptor 9-myeloid differentiation factor 88 signaling pathway activation in rats with ventilator-induced lung injury. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2018, 30(1): 13-17.
8. Zhang Y, Guallar E, Ashar FN, <italic>et al</italic>. Association between mitochondrial DNA copy number and sudden cardiac death: findings from the Atherosclerosis Risk in Communities study (ARIC). Eur Heart J, 2017, 38(46): 3443-3448.
9. Yue P, Jing S, Liu L, <italic>et al</italic>. Association between mitochondrial DNA copy number and cardiovascular disease: Current evidence based on a systematic review and meta-analysis. PLoS One, 2018, 13(11): e0206003.
10. Corsi S, Iodice S, Vigna L, <italic>et al</italic>. Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity. Clin Epigenetics, 2020, 12(1): 29.
11. Hu H, Lin Y, Xu X, <italic>et al</italic>. The alterations of mitochondrial DNA in coronary heart disease. Exp Mol Pathol, 2020, 114: 104412.
12. Liu LP, Cheng K, Ning MA, <italic>et al</italic>. Association between peripheral blood cells mitochondrial DNA content and severity of coronary heart disease. Atherosclerosis, 2017, 261: 105-110.
13. Chen S, Xie X, Wang Y, <italic>et al</italic>. Association between leukocyte mitochondrial DNA content and risk of coronary heart disease: A case-control study. Atherosclerosis, 2014, 237(1): 220-226.
14. Liu J, Cai X, Xie L, <italic>et al</italic>. Circulating cell free mitochondrial DNA is a biomarker in the development of coronary heart disease in the patients with type 2 diabetes. Clin Lab, 2015, 61(7): 661-667.
15. Liu J, Zou Y, Tang Y, <italic>et al</italic>. Circulating cell-free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus. J Diabetes Investig, 2016, 7(1): 109-114.
16. Bliksøen M, Mariero LH, Ohm IK, <italic>et al</italic>. Increased circulating mitochondrial DNA after myocardial infarction. Int J Cardiol, 2012, 158(1): 132-134.
17. Wang L, Xie L, Zhang Q, <italic>et al</italic>. Plasma nuclear and mitochondrial DNA levels in acute myocardial infarction patients. Coron Artery Dis, 2015, 26(4): 296-300.
18. Qin C, Gu J, Liu R, <italic>et al</italic>. Release of mitochondrial DNA correlates with peak inflammatory cytokines in patients with acute myocardial infarction. Anatol J Cardiol, 2017, 17(3): 224-228.
19. Lubkin DT, Bishawi M, Barbas AS, <italic>et al</italic>. Extracellular mitochondrial DNA and N-formyl peptides in trauma and critical illness: A systematic review. Crit Care Med, 2018, 46(12): 2018-2028.
20. Timmermans K, Kox M, Vaneker M, <italic>et al</italic>. Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients. Intensive Care Med, 2016, 42(4): 551-561.
21. Prikhodko AS, Shabanov AK, Zinovkina LA, <italic>et al</italic>. Pure mitochondrial DNA does not activate human neutrophils in vitro. Biochemistry (Mosc), 2015, 80(5): 629-635.
22. Kung CT, Hsiao SY, Tsai TC, <italic>et al</italic>. Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room. J Transl Med, 2012, 10: 130.
23. Bhagirath VC, Dwivedi DJ, Liaw PC. Comparison of the proinflammatory and procoagulant properties of nuclear, mitochondrial, and bacterial DNA. Shock, 2015, 44(3): 265-271.
24. Timmermans K, Kox M, Scheffer GJ, <italic>et al</italic>. Plasma nuclear and mitochondrial DNA Levels, and markers of inflammation, shock, and organ damage in patients with septic shock. Shock, 2016, 45(6): 607-612.
25. Lu CH, Chang WN, Tsai NW, <italic>et al</italic>. The value of serial plasma nuclear and mitochondrial DNA levels in adult community-acquired bacterial meningitis. QJM, 2010, 103(3): 169-175.
26. Garrabou G, Morén C, López S, <italic>et al</italic>. The effects of sepsis on mitochondria. J Infect Dis, 2012, 205(3): 392-400.
27. Di Caro V, Walko TD, Bola RA, <italic>et al</italic>. Plasma mitochondrial DNA--a novel DAMP in pediatric sepsis. Shock, 2016, 45(5): 506-511.
28. Gu X, Yao Y, Wu G, <italic>et al</italic>. The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome. PLoS One, 2013, 8(8): e72834.
29. Jansen MPB, Pulskens WP, Butter LM, <italic>et al</italic>. Mitochondrial DNA is released in urine of SIRS patients with acute kidney injury and correlates with severity of renal dysfunction. Shock, 2018, 49(3): 301-310.
30. Yu M. Circulating cell-free mitochondrial DNA as a novel cancer biomarker: Opportunities and challenges. Mitochondrial DNA, 2012, 23(5): 329-332.
31. Mohamed Yusoff AA, Mohd Nasir KN, Haris K, <italic>et al</italic>. Detection of somatic mutations in the mitochondrial DNA control region D-loop in brain tumors: The first report in Malaysian patients. Oncol Lett, 2017, 14(5): 5179-5188.
32. Mohamed Yusoff AA. Role of mitochondrial DNA mutations in brain tumors: A mini-review. J Cancer Res Ther, 2015, 11(3): 535-544.
33. Chang X, Bakay M, Liu Y, et al. Mitochondrial DNA haplogroups and susceptibility to neuroblastoma. J Natl Cancer Inst, 2020. [Epub ahead of print].
34. Meng S, De Vivo I, Liang L, <italic>et al</italic>. Pre-diagnostic leukocyte mitochondrial DNA copy number and risk of lung cancer. Oncotarget, 2016, 7(19): 27307-27312.
35. Nissanka N, Moraes CT. Mitochondrial DNA heteroplasmy in disease and targeted nuclease-based therapeutic approaches. EMBO Rep, 2020: e49612.
36. Harrington JS, Huh JW, Schenck EJ, <italic>et al</italic>. Circulating mitochondrial DNA as predictor of mortality in critically ill patients: A systematic review of clinical studies. Chest, 2019, 156(6): 1120-1136.
37. Nakahira K, Kyung SY, Rogers AJ, <italic>et al</italic>. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med, 2013, 10(12): e1001577.
38. Baysa A, Fedorov A, Kondratov K, <italic>et al</italic>. Release of mitochondrial and nuclear DNA during on-pump heart surgery: Kinetics and relation to extracellular vesicles. J Cardiovasc Transl Res, 2019, 12(3): 184-192.
39. 秦超毅, 古君, 钱宏, 等. 体外循环围手术期血液中线粒体 DNA 浓度变化. 中国胸心血管外科临床杂志, 2015, 22(3): 241-244.
40. Tabata S, Yamaguchi S, Nagamine H, <italic>et al</italic>. Efficacy of FK633, an ultra-short acting glycoproteinⅡb/Ⅲa antagonist on platelet preservation during and after cardiopulmonary bypass. Eur J Cardiothorac Surg, 2004, 26(2): 289-293.
41. Varon D, Shai E. Platelets and their microparticles as key players in pathophysiological responses. J Thromb Haemost, 2015, 13(Suppl 1): S40-S46.
42. Boudreau LH, Duchez AC, Cloutier N, <italic>et al</italic>. Platelets release mitochondria serving as substrate for bactericidal group ⅡA-secreted phospholipase A2 to promote inflammation. Blood, 2014, 124(14): 2173-2183.
43. Qin C, Gu J, Hu J, <italic>et al</italic>. Platelets activation is associated with elevated plasma mitochondrial DNA during cardiopulmonary bypass. J Cardiothorac Surg, 2016, 11(1): 90.
44. Aslami H, Beurskens CJP, Tuip AM, <italic>et al</italic>. Induced hypothermia is associated with reduced circulating subunits of mitochondrial DNA in cardiac arrest patients. Mitochondrial DNA A DNA Mapp Seq Anal, 2018, 29(4): 525-528.
45. Arnalich F, Codoceo R, López-Collazo E, <italic>et al</italic>. Circulating cell-free mitochondrial DNA: A better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation, 2012, 83(7): e162-163.
46. Krychtiuk KA, Wurm R, Ruhittel S, <italic>et al</italic>. Release of mitochondrial DNA is associated with mortality in severe acute heart failure. Eur Heart J Acute Cardiovasc Care, 2019: 2048872618823405.
47. Knez J, Lakota K, Božič N, <italic>et al</italic>. Correlation between mitochondrial DNA content measured in myocardium and peripheral blood of patients with non-ischemic heart failure. Genet Test Mol Biomarkers, 2017, 21(12): 736-741.

Previous Article
Mapping knowledge domains analysis of gastrointestinal stromal tumor research
Next Article
Analysis of therapeutic effects of 22 cases of mesenteric venous thrombosis

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress of mitochondrial DNA as a pathogenic factor in diseases

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content