Roles of Mitochondrial DNA Signaling in Immune Responses

  • Lingyan Wang
  • Michael N. Liebmen
  • Xiangdong WangEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1038)


Mitochondrial DNA (mtDNA) plays an important role in immune responses during the evolution. The present chapter systemically describes its role on immune-related diseases and its interaction on immune responses. It is important to explore the main function and mechanisms of mtDNA in immune responses by which mtDNA regulates the signaling pathways of Toll-like receptor 9, autophagy, and STING. There are potentials to discover therapeutic targets of mtDNA in immune diseases and inflammation. It will be more exciting if the CRISPR-Cas9 method can be applied for mtDNA gene editing to cure diseases and provide a novel insight of mtDNA in immune responses as well as new therapies.


mtDNA Immune responses TLR9 Autophagy STING CRISPR-Cas9 



Acute lung injury


Cardiopulmonary bypass


Prokaryotic type II clustered regularly interspaced short palindromic repeats-CRISPR-associated 9


Damage-associated molecular patterns


High-mobility group protein B1


Interferon regulatory factor 7


Immune-related pancytopenia


Interferon-stimulated genes


Microtubule-associated protein1 light chain 3B


Mitogen-activated protein kinases


Stroke-like episodes


Mitochondrial permeability transition


Mitochondrial DNA


Response protein 88


Nonalcoholic fatty liver disease


Nuclear DNA


Neutrophil extracellular traps


Nuclear factor-κB


Oxidative phosphorylation


Polymorphonuclear neutrophils


Rheumatoid arthritis


Reactive oxygen species


Spontaneously hypertensive rats


Toll-like receptor 9



The work was supported by Zhongshan Distinguished Professor Grant (XDW), the National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81300010), the Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600, 14431905100), Operation funding of Shanghai Institute of Clinical Bioinformatics, Ministry of Education for Academic Special Science and Research Foundation for PhD Education (20130071110043), and National Key Research and Development Program (2016YFC0902400, 2017YFSF090207).

Conflict of Interest

The authors declare no conflict of interest.


  1. 1.
    Finsterer J, Zarrouk-Mahjoub S. Is chronic fatigue syndrome truly associated with haplogroups or mtDNA single nucleotide polymorphisms? J Transl Med. 2016;14:182. PubMed:27317438CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Zhu LZ, Hou YJ, Zhao M, Yang MF, XT F, Sun JY, et al. Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation. Cell Biol Toxicol. 2016;32:333–45. PubMed:27184666CrossRefPubMedGoogle Scholar
  3. 3.
    Opperman CM, Sishi BJ. Tumor necrosis factor alpha stimulates p62 accumulation and enhances proteasome activity independently of ROS. Cell Biol Toxicol. 2015;31:83–94. PubMed:25761618CrossRefPubMedGoogle Scholar
  4. 4.
    Ribas V, Garcia-Ruiz C, Fernandez-Checa JC. Mitochondria, cholesterol and cancer cell metabolism. Clin Transl Med. 2016;5:22. PubMed:27455839CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Zerin T, Kim JS, Gil HW, Song HY, Hong SY. Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells. Cell Biol Toxicol. 2015;31:261–72. PubMed:26728267CrossRefPubMedGoogle Scholar
  6. 6.
    Khan NA, Nikkanen J, Yatsuga S, Jackson C, Wang L, Pradhan S, et al. mTORC1 regulates mitochondrial integrated stress response and mitochondrial myopathy progression. Cell Metab. 2017;26:419–28 e5. PubMed:28768179CrossRefPubMedGoogle Scholar
  7. 7.
    Kodron A, Ghanim M, Krawczyk KK, Stelmaszczyk-Emmel A, Tonska K, Demkow U, et al. Mitochondrial DNA in pediatric leukemia patients. Acta Biochim Pol. 2017;64:183–7. PubMed:28284021CrossRefPubMedGoogle Scholar
  8. 8.
    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. PubMed:15583871CrossRefPubMedGoogle Scholar
  9. 9.
    Ganta KK, Mandal A, Chaubey B. Depolarization of mitochondrial membrane potential is the initial event in non-nucleoside reverse transcriptase inhibitor efavirenz induced cytotoxicity. Cell Biol Toxicol. 2017;33:69–82. PubMed:27639578CrossRefPubMedGoogle Scholar
  10. 10.
    Hammerling BC, Shires SE, Leon LJ, Cortez MQ, Gustafsson AB. Isolation of Rab5-positive endosomes reveals a new mitochondrial degradation pathway utilized by BNIP3 and Parkin. Small GTPases. 2017:1–8. PubMed:28696827Google Scholar
  11. 11.
    Meng N, Han L, Pan X, Su L, Jiang Z, Lin Z, et al. Nano-Mg(OH)2-induced proliferation inhibition and dysfunction of human umbilical vein vascular endothelial cells through caveolin-1-mediated endocytosis. Cell Biol Toxicol. 2015;31:15–27. PubMed:25575676CrossRefPubMedGoogle Scholar
  12. 12.
    Bao W, Xia H, Liang Y, Ye Y, Lu Y, Xu X, et al. Toll-like receptor 9 can be activated by endogenous mitochondrial DNA to induce podocyte apoptosis. Sci Rep. 2016;22579:6. PubMed:26934958Google Scholar
  13. 13.
    EP Y, Bennett MR. Mitochondrial DNA damage and atherosclerosis. Trends Endocrinol Metab. 2014;25:481–7. PubMed:25034130CrossRefGoogle Scholar
  14. 14.
    Kikuchi S, Ninomiya T, Kohno T, Kojima T, Tatsumi H. Cobalt inhibits motility of axonal mitochondria and induces axonal degeneration in cultured dorsal root ganglion cells of rat. Cell Biol Toxicol. 2017. PubMed:28656345
  15. 15.
    Giromini C, Rebucci R, Fusi E, Rossi L, Saccone F, Baldi A. Cytotoxicity, apoptosis, DNA damage and methylation in mammary and kidney epithelial cell lines exposed to ochratoxin A. Cell Biol Toxicol. 2016;32:249–58. PubMed:27154019CrossRefPubMedGoogle Scholar
  16. 16.
    Vedi M, Sabina EP. Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation. Cell Biol Toxicol. 2016;32:373–90. PubMed:27250656CrossRefPubMedGoogle Scholar
  17. 17.
    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. PubMed:20203610CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon HU. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ. 2009;16:1438–44. PubMed:19609275CrossRefPubMedGoogle Scholar
  19. 19.
    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. PubMed:25128442Google Scholar
  20. 20.
    Venkatesan T, Choi YW, Mun SP, Kim YK. Pinus radiata bark extract induces caspase-independent apoptosis-like cell death in MCF-7 human breast cancer cells. Cell Biol Toxicol. 2016;32:451–64. PubMed:27400986CrossRefPubMedGoogle Scholar
  21. 21.
    Medvedev R, Hildt E, Ploen D. Look who’s talking-the crosstalk between oxidative stress and autophagy supports exosomal-dependent release of HCV particles. Cell Biol Toxicol. 2017;33:211–31. PubMed:27987184CrossRefPubMedGoogle Scholar
  22. 22.
    Morshed M, Hlushchuk R, Simon D, Walls AF, Obata-Ninomiya K, Karasuyama H, et al. NADPH oxidase-independent formation of extracellular DNA traps by basophils. J Immunol. 2014;192:5314–23. PubMed:24771850CrossRefPubMedGoogle Scholar
  23. 23.
    Meller S, Di Domizio J, Voo KS, Friedrich HC, Chamilos G, Ganguly D, et al. T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nat Immunol. 2015;16:970–9. PubMed:26168081CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Collins LV, Hajizadeh S, Holme E, Jonsson IM, Tarkowski A. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses. J Leukoc Biol. 2004;75:995–1000. PubMed:14982943CrossRefPubMedGoogle Scholar
  25. 25.
    Seo JB, Jung SR, Hille B, Koh DS, Extracellular ATP. protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y1 receptor-cAMP signal pathway. Cell Biol Toxicol. 2016;32:229–47. PubMed:27197531CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    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. PubMed:25642965CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Di Caro V, Walko TD 3rd, Bola RA, Hong JD, Pang D, Hsue V, et al. Plasma mitochondrial DNA – a novel DAMP in pediatric sepsis. Shock. 2016;45:506–11. PubMed:26682947CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature. 2012;485:251–5. PubMed:22535248CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Marques PE, Amaral SS, Pires DA, Nogueira LL, Soriani FM, Lima BH, et al. Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure. Hepatology. 2012;56:1971–82. PubMed:22532075CrossRefPubMedGoogle Scholar
  30. 30.
    Kaarniranta K, Tokarz P, Koskela A, Paterno J, Blasiak J. Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration. Cell Biol Toxicol. 2017;33:113–28. PubMed:27900566CrossRefPubMedGoogle Scholar
  31. 31.
    Celardo I, Martins LM, Gandhi S. Unravelling mitochondrial pathways to Parkinson’s disease. Br J Pharmacol. 2014;171:1943–57. PubMed:24117181CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lin C, Chen S, Li Y. T cell modulation in immunotherapy for hematological malignancies. Cell Biol Toxicol. 2017;33:323–7. PubMed:28474249CrossRefPubMedGoogle Scholar
  33. 33.
    Berridge MV, Dong L, Neuzil J. Mitochondrial DNA in tumor initiation, progression, and metastasis: role of horizontal mtDNA transfer. Cancer Res. 2015;75:3203–8. PubMed:26224121CrossRefPubMedGoogle Scholar
  34. 34.
    Pasquier J, Guerrouahen BS, Al Thawadi H, Ghiabi P, Maleki M, Abu-Kaoud N, et al. Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance. J Transl Med. 2013;11:94. PubMed:23574623CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Bai L, Chen W, Chen J, Li W, Zhou L, Niu C, et al. Heterogeneity of toll-like receptor 9 signaling in B cell malignancies and its potential therapeutic application. J Transl Med. 2017;51:15. PubMed:28241765Google Scholar
  36. 36.
    Barber GN. Cytoplasmic DNA innate immune pathways. Immunol Rev. 2011;243:99–108. PubMed:21884170CrossRefPubMedGoogle Scholar
  37. 37.
    He Y, Feng D, Li M, Gao Y, Ramirez T, Cao H, et al. Hepatic mitochondrial DNA/Toll-like receptor 9/MicroRNA-223 forms a negative feedback loop to limit neutrophil overactivation and acetaminophen hepatotoxicity in mice. Hepatology. 2017;220-34:66. PubMed:28295449Google Scholar
  38. 38.
    Zhang L, Deng S, Zhao S, Ai Y, Pan P, Su X, et al. Intra-peritoneal administration of mitochondrial DNA provokes acute lung injury and systemic inflammation via toll-like receptor 9. Int J Mol Sci. 2016;17:1425. PubMed:27589725CrossRefPubMedCentralGoogle Scholar
  39. 39.
    Tsuji N, Tsuji T, Ohashi N, Kato A, Fujigaki Y, Yasuda H. Role of mitochondrial DNA in septic AKI via toll-like receptor 9. J Am Soc Nephrol. 2016;27:2009–20. PubMed:26574043CrossRefPubMedGoogle Scholar
  40. 40.
    Schafer ST, Franken L, Adamzik M, Schumak B, Scherag A, Engler A, et al. Mitochondrial DNA: an endogenous trigger for immune paralysis. Anesthesiology. 2016;124:923–33. PubMed:26808636CrossRefPubMedGoogle Scholar
  41. 41.
    McCarthy CG, Wenceslau CF, Goulopoulou S, Ogbi S, Baban B, Sullivan JC, et al. Circulating mitochondrial DNA and Toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats. Cardiovasc Res. 2015;119-30:107. PubMed:25910936Google Scholar
  42. 42.
    Bliksoen M, Mariero LH, Torp MK, Baysa A, Ytrehus K, Haugen F, et al. Extracellular mtDNA activates NF-kappaB via toll-like receptor 9 and induces cell death in cardiomyocytes. Basic Res Cardiol. 2016;42:111. PubMed:27164906Google Scholar
  43. 43.
    Gu X, Wu G, Yao Y, Zeng J, Shi D, Lv T, et al. Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway. Free Radic Biol Med. 2015;83:149–58. PubMed:25772007CrossRefPubMedGoogle Scholar
  44. 44.
    Sandler N, Kaczmarek E, Itagaki K, Zheng Y, Otterbein L, Khabbaz K, et al. Mitochondrial DAMPs are released during cardiopulmonary bypass surgery and are associated with postoperative atrial fibrillation. Heart Lung Circ. 2017. PubMed:28487062
  45. 45.
    Zhang Q, Itagaki K, Hauser CJ. Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase. Shock. 2010;34:55–9. PubMed:19997055CrossRefPubMedGoogle Scholar
  46. 46.
    Wang X. New biomarkers and therapeutics can be discovered during COPD-lung cancer transition. Cell Biol Toxicol. 2016;32:359–61. PubMed:27405768CrossRefPubMedGoogle Scholar
  47. 47.
    Chen C, Shi L, Li Y, Wang X, Yang S. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia. Cell Biol Toxicol. 2016;32:169–84. PubMed:27095254CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Arumugam P, Samson A, Ki J, Song JM. Knockdown of clusterin alters mitochondrial dynamics, facilitates necrosis in camptothecin-induced cancer stem cells. Cell Biol Toxicol. 2017;33:307–21. PubMed:28064403CrossRefPubMedGoogle Scholar
  49. 49.
    Lippai M, Szatmari Z. Autophagy-from molecular mechanisms to clinical relevance. Cell Biol Toxicol. 2017;33:145–68. PubMed:27957648CrossRefPubMedGoogle Scholar
  50. 50.
    Zhang Z, Meng P, Han Y, Shen C, Li B, Hakim MA, et al. Mitochondrial DNA-LL-37 complex promotes atherosclerosis by escaping from autophagic recognition. Immunity. 2015;1137-47:43. PubMed:26680206Google Scholar
  51. 51.
    Carlos D, Costa FR, Pereira CA, Rocha FA, Yaochite JN, Oliveira GG, et al. Mitochondrial DNA activates the NLRP3 inflammasome and predisposes to type 1 diabetes in Murine model. Front Immunol. 2017;8:164. PubMed:28289409CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Denardin CC, Martins LA, Parisi MM, Vieira MQ, Terra SR, Barbe-Tuana FM, et al. Autophagy induced by purple pitanga (Eugenia uniflora L.) extract triggered a cooperative effect on inducing the hepatic stellate cell death. Cell Biol Toxicol. 2017;33:197–206. PubMed:27744523CrossRefPubMedGoogle Scholar
  53. 53.
    Cao C, Wang W, Lu L, Wang L, Chen X, Guo R, et al. Inactivation of Beclin-1-dependent autophagy promotes ursolic acid-induced apoptosis in hypertrophic scar fibroblasts. Exp Dermatol. 2017. PubMed:28767174
  54. 54.
    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. PubMed:21151103CrossRefPubMedGoogle Scholar
  55. 55.
    Rodgers MA, Bowman JW, Liang Q, Jung JU. Regulation where autophagy intersects the inflammasome. Antioxid Redox Signal. 2014;20:495–506. PubMed:23642014CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Unuma K, Aki T, Funakoshi T, Hashimoto K, Uemura K. Extrusion of mitochondrial contents from lipopolysaccharide-stimulated cells: Involvement of autophagy. Autophagy. 2015;11:1520–36. PubMed:26102061CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Liu S, Zhang Y, Ren J, Li J. Microbial DNA recognition by cGAS-STING and other sensors in dendritic cells in inflammatory bowel diseases. Inflamm Bowel Dis. 2015;21:901–11. PubMed:25581829CrossRefPubMedGoogle Scholar
  58. 58.
    Rongvaux A, Jackson R, Harman CC, Li T, West AP, de Zoete MR, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159:1563–77. PubMed:25525875CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Zhang X, Yin H, Li Z, Zhang T, Yang Z. Nano-TiO2 induces autophagy to protect against cell death through antioxidative mechanism in podocytes. Cell Biol Toxicol. 2016;32:513–27. PubMed:27430495CrossRefPubMedGoogle Scholar
  60. 60.
    Yuan L, Mao Y, Luo W, Wu W, Xu H, Wang XL, et al. Palmitic acid dysregulates the Hippo-YAP pathway and inhibits angiogenesis by inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS-STING-IRF3 signaling. J Biol Chem. 2017. PubMed:28698384
  61. 61.
    Mao Y, Luo W, Zhang L, Wu W, Yuan L, Xu H, et al. STING-IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage in diet-induced obesity. Arterioscler Thromb Vasc Biol. 2017;37:920–9. PubMed:28302626CrossRefPubMedGoogle Scholar
  62. 62.
    Zhu D, Liu Z, Pan Z, Qian M, Wang L, Zhu T, et al. A new method for classifying different phenotypes of kidney transplantation. Cell Biol Toxicol. 2016;32:323–32. PubMed:27278387CrossRefPubMedGoogle Scholar
  63. 63.
    Biacchesi S, Merour E, Lamoureux A, Bernard J, Bremont M. Both STING and MAVS fish orthologs contribute to the induction of interferon mediated by RIG-I. PLoS One. 2012;7:e47737. PubMed:23091644CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    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. PubMed:25525874CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Petrasek J, Iracheta-Vellve A, Csak T, Satishchandran A, Kodys K, Kurt-Jones EA, et al. STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease. Proc Natl Acad Sci U S A. 2013;110:16544–9. PubMed:24052526CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Onuora S. Autoinflammation: a new STING-associated monogenic autoinflammatory disease. Nat Rev Rheumatol. 2014;10:512. PubMed:25090944CrossRefPubMedGoogle Scholar
  67. 67.
    Li XD, Wu J, Gao D, Wang H, Sun L, Chen ZJ. Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science. 2013;341:1390–4. PubMed:23989956CrossRefPubMedGoogle Scholar
  68. 68.
    Gao D, Wu J, YT W, 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. PubMed:23929945CrossRefPubMedGoogle Scholar
  69. 69.
    Wu B, Ni H, Li J, Zhuang X, Zhang J, Qi Z, et al. The impact of circulating mitochondrial DNA on cardiomyocyte apoptosis and myocardial injury after TLR4 activation in experimental autoimmune myocarditis. Cell Physiol Biochem. 2017;42:713–28. PubMed:28618428CrossRefPubMedGoogle Scholar
  70. 70.
    Xie L, Liu S, Cheng J, Wang L, Liu J, Gong J. Exogenous administration of mitochondrial DNA promotes ischemia reperfusion injury via TLR9-p38 MAPK pathway. Regul Toxicol Pharmacol. 2017;89:148–54. PubMed:28757323CrossRefPubMedGoogle Scholar
  71. 71.
    Duvvuri B, Duvvuri VR, Wang C, Chen L, Wagar LE, Jamnik V, et al. The human immune system recognizes neopeptides derived from mitochondrial DNA deletions. J Immunol. 2014;192:4581–91. PubMed:24733843CrossRefPubMedGoogle Scholar
  72. 72.
    Zhou QF, SM X, Wang HQ, Xing LM, Fu R, Shao ZH. Single nucleotide polymorphism of mitochondrial DNA D-LOOP region in peripheral blood lymphocytes of immuno-related pancytopenia patients. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017;25:186–91. PubMed:28245399PubMedGoogle Scholar
  73. 73.
    Wang W, Zhuang Q, Ji K, Wen B, Lin P, Zhao Y, et al. Identification of miRNA, lncRNA and mRNA-associated ceRNA networks and potential biomarker for MELAS with mitochondrial DNA A3243G mutation. Sci Rep. 2017;7:41639. PubMed:28139706CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Imanishi H, Takibuchi G, Kobayashi T, Ishikawa K, Nakada K, Mori M, et al. Specific mtDNA mutations in mouse carcinoma cells suppress their tumor formation via activation of the host innate immune system. PLoS One. 2013;8:e75981. PubMed:24098752CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Feng S, Xiong L, Ji Z, Cheng W, Yang H. Correlation between increased ND2 expression and demethylated displacement loop of mtDNA in colorectal cancer. Mol Med Rep. 2012;6:125–30. PubMed:22505229PubMedGoogle Scholar
  76. 76.
    Fang H, Wang W. Could CRISPR be the solution for gene editing’s Gordian knot? Cell Biol Toxicol. 2016;32:465–7. PubMed:27614448CrossRefPubMedGoogle Scholar
  77. 77.
    Wang W, Wang X. Single-cell CRISPR screening in drug resistance. Cell Biol Toxicol. 2017;33:207–10. PubMed:28474250CrossRefPubMedGoogle Scholar
  78. 78.
    Paes B, Moco PD, Pereira CG, Porto GS, de Sousa Russo EM, Reis LCJ, et al. Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation. Cell Biol Toxicol. 2017;33:233–50. PubMed:28039590CrossRefPubMedGoogle Scholar
  79. 79.
    Arroyo JD, Jourdain AA, Calvo SE, Ballarano CA, Doench JG, Root DE, et al. A genome-wide CRISPR death screen identifies genes essential for oxidative phosphorylation. Cell Metab. 2016;24:875–85. PubMed:27667664CrossRefPubMedGoogle Scholar
  80. 80.
    Luo C, Lim JH, Lee Y, Granter SR, Thomas A, Vazquez F, et al. A PGC1alpha-mediated transcriptional axis suppresses melanoma metastasis. Nature. 2016;537:422–6. PubMed:27580028CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Editor(s) (if applicable) and The Author(s) 2018 2017

Authors and Affiliations

  • Lingyan Wang
    • 1
    • 2
  • Michael N. Liebmen
    • 1
    • 2
  • Xiangdong Wang
    • 3
    Email author
  1. 1.Zhongshan Hospital Institute of Clinical ScienceFudan UniversityShanghaiChina
  2. 2.Shanghai Institute of Clinical Bioinformatics, Biomedical Research CenterShanghaiChina
  3. 3.Zhongshan Hospital Institute of Clinical Science, Fudan UniversityShanghai Medical CollegeShanghaiChina

Personalised recommendations