Skip to main content
Log in

Mitochondrial Epigenetics and Environmental Exposure

  • Environmental Epigenetics (A Baccarelli, Section Editor)
  • Published:
Current Environmental Health Reports Aims and scope Submit manuscript

Abstract

The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of Particular Interest, Published recently, Have Been Highlighted as: • Of Importance •• Of Major Importance

  1. Papa S, Martino PL, Capitanio G, Gaballo A, De Rasmo D, Signorile A, et al. The oxidative phosphorylation system in mammalian mitochondria. Adv Exp Med Biol. 2012;942:3–37.

    Article  CAS  PubMed  Google Scholar 

  2. Cali T, Ottolini D, Brini M. Mitochondrial Ca(2+) as a key regulator of mitochondrial activities. Adv Exp Med Biol. 2012;942:53–73.

    Article  CAS  PubMed  Google Scholar 

  3. Antico Arciuch VG, Elguero ME, Poderoso JJ, Carreras MC. Mitochondrial regulation of cell cycle and proliferation. Antioxid Redox Signal. 2012;16(10):1150–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Byun HM, Panni T, Motta V, Hou L, Nordio F, Apostoli P, et al. Effects of airborne pollutants on mitochondrial DNA methylation. Part Fibre Toxicol. 2013;10(1):18 .mtDNA methylation associated with environmental exposure.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen L, Yoo SE, Na R, Liu Y, Ran Q. Cognitive impairment and increased Abeta levels induced by paraquat exposure are attenuated by enhanced removal of mitochondrial H(2)O(2). Neurobiol Aging. 2012;33(2):432 e15–26.

    Article  PubMed  Google Scholar 

  6. Lambertini L, Chen J, Nomura Y. Mitochondrial Gene expression profiles are associated with maternal psychosocial stress in pregnancy and infant temperament. PLoS One. 2015;10(9):e0138929.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Meyer JN, Leung MC, Rooney JP, Sendoel A, Hengartner MO Kisby GE, et al. Mitochondria as a target of environmental toxicants. Toxic Sci. 2013.

  8. Pavanello S, Dioni L, Hoxha M, Fedeli U, Mielzynska-Svach D, Baccarelli AA. Mitochondrial DNA copyn and exposure to polycyclic aromatic hydrocarbons. Cancer Epidemiol Biomarkers Prev. 2013.

  9. Pieters N, Koppen G, Smeets K, Napierska D, Plusquin M, De Prins S, et al. Decreased mitochondrial DNA content in association with exposure to polycyclic aromatic hydrocarbons in house dust during wintertime: from a population enquiry to cell culture. PLoS One. 2013;8(5):e63208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pshenichnyuk SA, Modelli A. Can mitochondrial dysfunction be initiated by dissociative electron attachment to xenobiotics? Phys Chem Chem Phys. 2013.

  11. Hirano A, Donnenfeld H, Sasaki S, Nakano I. Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 1984;43(5):461–70.

    Article  CAS  PubMed  Google Scholar 

  12. Masui Y, Mozai T, Kakehi K. Functional and morphometric study of the liver in motor neuron disease. J Neurol. 1985;232(1):15–9.

    Article  CAS  PubMed  Google Scholar 

  13. Ogata T, Yamasaki Y. Ultra-high-resolution scanning electron microscopy of mitochondria and sarcoplasmic reticulum arrangement in human red, white, and intermediate muscle fibers. Anat Rec. 1997;248(2):214–23.

    Article  CAS  PubMed  Google Scholar 

  14. Sagan L. On the origin of mitosing cells. J Theor Biol. 1967;14(3):255–74.

    Article  CAS  PubMed  Google Scholar 

  15. William M, Roettger M, Kloesges T, Thiergart T, Woehle C, Gould C, et al. Modern endosymbiotic theory: getting lateral gene transfer in-to the eq. J Endocytob Cell Res 2012;23:1–5.

  16. Mishra P, Chan DC. Mitochondrial dynamics and inheritance during cell division, development and disease. Nat Rev Mol Cell Biol. 2014;15(10):634–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ye K, Lu J, Ma F, Keinan A, Gu Z. Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals. Proc Natl Acad Sci U S A. 2014;111(29):10654–9 .Thorough investigation on the prevelance of mitochondrial heteroplasmy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J. 2003;17(10):1195–214.

    Article  CAS  PubMed  Google Scholar 

  19. Mambo E, Gao X, Cohen Y, Guo Z, Talalay P, Sidransky D. Electrophile and oxidant damage of mitochondrial DNA leading to rapid evolution of homoplasmic mutations. Proc Natl Acad Sci U S A. 2003;100(4):1838–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chinnery PF. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al. editors. Gene Reviews(R). Seattle; 1993.

  21. Dawid IB. 5-methylcytidylic acid: absence from mitochondrial DNA of frogs and HeLa cells. Science. 1974;184(4132):80–1.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

  23. Bogenhagen DF. Mitochondrial DNA nucleoid structure. Biochim Biophys Acta 2012;1819(9–10):914–920.

  24. Gilkerson R, Bravo L, Garcia I, Gaytan N, Herrera A, Maldonado A, et al. The mitochondrial nucleoid: integrating mitochondrial DNA into cellular homeostasis. Cold Spring Harb Perspect Biol. 2013;5(5).

  25. Rebelo AP, Dillon LM, Moraes CT. Mitochondrial DNA transcription regulation and nucleoid organization. J Inherit Metab Dis. 2011;34(4):941–51.

    Article  CAS  PubMed  Google Scholar 

  26. Bandiera S, Ruberg S, Girard M, Cagnard N, Hanein S, Chretien D, et al. Nuclear outsourcing of RNA interference components to human mitochondria. PLoS One. 2011;6(6):e20746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Burzio VA, Villota C, Villegas J, Landerer E, Boccardo E, Villa LL, et al. Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells. Proc Natl Acad Sci U S A. 2009;106(23):9430–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shock LS, Thakkar PV, Peterson EJ, Moran RG, Taylor SM. DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011;108(9):3630–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009;23(7):781–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nass MM. Differential methylation of mitochondrial and nuclear DNA in cultured mouse, hamster and virus-transformed hamster cells. In vivo and in vitro methylation. J Mol Biol. 1973;80(1):155–75.

    Article  CAS  PubMed  Google Scholar 

  31. Pollack Y, Kasir J, Shemer R, Metzger S, Szyf M. Methylation pattern of mouse mitochondrial DNA. Nucleic Acids Res. 1984;12(12):4811–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shmookler Reis RJ, Goldstein S. Mitochondrial DNA In mortal and immortal human cells. Genome number, integrity, and methylation. J Biol Chem 1983;258(15):9078–9085.

  33. Dzitoyeva S, Chen H, Manev H. Effect of aging on 5-hydroxymethylcytosine in brain mitochondria. Neurobiol Aging. 2012;33(12):2881–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Infantino V, Castegna A, Iacobazzi F, Spera I, Scala I, Andria G, et al. Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome. Mol Genet Metab. 2011;102(3):378–82.

    Article  CAS  PubMed  Google Scholar 

  35. Fisher RP, Clayton DA. Purification and characterization of human mitochondrial transcription factor 1. Mol Cell Biol. 1988;8(8):3496–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kaufman BA, Durisic N, Mativetsky JM, Costantino S, Hancock MA, Grutter P, et al. The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures. Mol Biol Cell. 2007;18(9):3225–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Legros F, Malka F, Frachon P, Lombes A, Rojo M. Organization and dynamics of human mitochondrial DNA. J Cell Sci. 2004;117(Pt 13):2653–62.

    Article  CAS  PubMed  Google Scholar 

  38. Mercer TR, Neph S, Dinger ME, Crawford J, Smith MA, Shearwood AM, et al. The human mitochondrial transcriptome. Cell. 2011;146(4):645–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921.

    Article  CAS  PubMed  Google Scholar 

  40. Wakeley J. The excess of transitions among nucleotide substitutions: new methods of estimating transition bias underscore its significance. Trends Ecol Evol. 1996;11(4):158–62.

    Article  CAS  PubMed  Google Scholar 

  41. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell - 4th edition. New York: Garland Science; 2002. p. 767–830.

    Google Scholar 

  42. Hou L, Zhang X, Dioni L, Barretta F, Dou C, Zheng Y, et al. Inhalable particulate matter and mitochondrial DNA copy number in highly exposed individuals in Beijing, China: a repeated-measure study. Part Fibre Toxicol. 2013;10(1):17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li H, Liu D, Lu J, Bai Y. Physiology and pathophysiology of mitochondrial DNA. Adv Exp Med Biol. 2012;942:39–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ramos A, Barbena E, Mateiu L, del Mar GM, Mairal Q, Lima M, et al. Nuclear insertions of mitochondrial origin: database updating and usefulness in cancer studies. Mitochondrion. 2011;11(6):946–53.

    Article  CAS  PubMed  Google Scholar 

  45. Richly E, Leister D. NUMTs in sequenced eukaryotic genomes. Mol Biol Evol. 2004;21(6):1081–4.

    Article  CAS  PubMed  Google Scholar 

  46. Schmitz J, Piskurek O, Zischler H. Forty million years of independent evolution: a mitochondrial gene and its corresponding nuclear pseudogene in primates. J Mol Evol. 2005;61(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  47. Jayaprakash AD, Benson EK, Gone S, Liang R, Shim J, Lambertini L, et al. Stable heteroplasmy at the single-cell level is facilitated by intercellular exchange of mtDNA. Nucleic Acids Res. 2015;43(4):2177–87 .First attempt to develop a technique that can make easy and scalable the extraction of pure mtDNA from total DNA extractions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Villegas J, Araya P, Bustos-Obregon E, Burzio LO. Localization of the 16S mitochondrial rRNA in the nucleus of mammalian spermatogenic cells. Mol Hum Reprod. 2002;8(11):977–83.

    Article  CAS  PubMed  Google Scholar 

  49. Villegas J, Muller I, Arredondo J, Pinto R, Burzio LO. A putative RNA editing from U to C in a mouse mitochondrial transcript. Nucleic Acids Res. 2002;30(9):1895–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Villegas J, Zarraga AM, Muller I, Montecinos L, Werner E, Brito M, et al. A novel chimeric mitochondrial RNA localized in the nucleus of mouse sperm. DNA Cell Biol. 2000;19(9):579–88.

    Article  CAS  PubMed  Google Scholar 

  51. Vidaurre S, Fitzpatrick C, Burzio VA, Briones M, Villota C, Villegas J, et al. Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy. J Biol Chem. 2014;289(39):27182–98 .One of the first thorough investigation on mtlncRNAs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Villota C, Campos A, Vidaurre S, Oliveira-Cruz L, Boccardo E, Burzio VA, et al. Expression of mitochondrial non-coding RNAs (ncRNAs) is modulated by high risk human papillomavirus (HPV) oncogenes. J Biol Chem. 2012;287(25):21303–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Volpi S, Bongiorni S, Fabbretti F, Wakimoto BT, Prantera G. Drosophila rae1 is required for male meiosis and spermatogenesis. J Cell Sci. 2013;126(Pt 16):3541–51.

    Article  CAS  PubMed  Google Scholar 

  54. Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013;50(1):R11–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Anderson DD, Quintero CM, Stover PJ. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011;108(37):15163–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.

    Article  CAS  PubMed  Google Scholar 

  57. Anandakumar S, Vijayakumar S, Arumugam N, Gromiha MM. Mammalian mitochondrial ncRNA database. Bioinformation. 2015;11(11):512–3.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Bianchessi V, Badi I, Bertolotti M, Nigro P, D'Alessandra Y, Capogrossi MC, et al. The mitochondrial lncRNA ASncmtRNA-2 is induced in aging and replicative senescence in endothelial cells. J Mol Cell Cardiol. 2015;81:62–70 .Intiguing study on the role of mitochondrial miRNAs and lncRNAs.

    Article  CAS  PubMed  Google Scholar 

  59. Kren BT, Wong PY, Sarver A, Zhang X, Zeng Y, Steer CJ. MicroRNAs identified in highly purified liver-derived mitochondria may play a role in apoptosis. RNA Biol. 2009;6(1):65–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Barrey E, Saint-Auret G, Bonnamy B, Damas D, Boyer O, Gidrol X. Pre-microRNA and mature microRNA in human mitochondria. PLoS One. 2011;6(5):e20220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Duarte FV, Palmeira CM, Rolo AP. The role of microRNAs in mitochondria: small players acting wide. Genes (Basel). 2014;5(4):865–86.

    Google Scholar 

  62. Kukat C, Wurm CA, Spahr H, Falkenberg M, Larsson NG, Jakobs S. Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA. Proc Natl Acad Sci U S A. 2011;108(33):13534–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bandiera S, Mategot R, Girard M, Demongeot J, Henrion-Caude A. MitomiRs delineating the intracellular localization of microRNAs at mitochondria. Free Radic Biol Med. 2013;64:12–9.

    Article  CAS  PubMed  Google Scholar 

  64. Duarte FV, Amorim JA, Palmeira CM, Rolo AP. Regulation of mitochondrial function and its impact in metabolic stress. Curr Med Chem. 2015.

  65. Berdanier CD. Mitochondrial gene expression: influence of nutrients and hormones. Exp Biol Med (Maywood). 2006;231(10):1593–601.

    CAS  Google Scholar 

  66. Cannino G, Di Liegro CM, Rinaldi AM. Nuclear-mitochondrial interaction. Mitochondrion. 2007;7(6):359–66.

    Article  CAS  PubMed  Google Scholar 

  67. Demonacos C, Djordjevic-Markovic R, Tsawdaroglou N, Sekeris CE. The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements. J Steroid Biochem Mol Biol. 1995;55(1):43–55.

    Article  CAS  PubMed  Google Scholar 

  68. Du J, Wang Y, Hunter R, Wei Y, Blumenthal R, Falke C, et al. Dynamic regulation of mitochondrial function by glucocorticoids. Proc Natl Acad Sci U S A. 2009;106(9):3543–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mabalirajan U, Ghosh B. Mitochondrial dysfunction in metabolic syndrome and asthma. J Allergy (Cairo). 2013;2013:340476.

    Google Scholar 

  70. Kim KH, Kabir E, Kabir S. A review on the human health impact of airborne particulate matter. Environ Int. 2015;74:136–43.

    Article  CAS  PubMed  Google Scholar 

  71. Shen H, Laird PW. Interplay between the cancer genome and epigenome. Cell. 2013;153(1):38–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Janssen BG, Byun HM, Gyselaers W, Lefebvre W, Baccarelli AA, Nawrot TS. Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: an ENVIRONAGE birth cohort study. Epigenetics. 2015;10(6):536–44 .Interesting study investigating mtDNA methylation and copy number at the same time.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008;4(2):89–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Miro O, Alonso JR, Jarreta D, Casademont J, Urbano-Marquez A, Cardellach F. Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes. Carcinogenesis. 1999;20(7):1331–6.

    Article  CAS  PubMed  Google Scholar 

  75. Elliott HR, Tillin T, McArdle WL, Ho K, Duggirala A, Frayling TM, et al. Differences in smoking associated DNA methylation patterns in south Asians and Europeans. Clin Epigenetics. 2014;6(1):4.

  76. Gao X, Jia M, Zhang Y, Breitling LP, Brenner H. DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies. Clin Epigenetics. 2015;7:113.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med. 2009;180(5):462–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Farina M, Avila DS, da Rocha JB, Aschner M. Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int. 2013;62(5):575–94.

    Article  CAS  PubMed  Google Scholar 

  79. Hou L, Zhu ZZ, Zhang X, Nordio F, Bonzini M, Schwartz J, et al. Airborne particulate matter and mitochondrial damage: a cross-sectional study. Environ Health. 2010;9:48.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Linqing Y, Bo X, Xueqin Y, Hong D, Desheng W, Huimin Z, et al. Mitochondrial DNA hypomethylation in chrome plating workers. Toxicol Lett. 2016;243:1–6.

    Article  Google Scholar 

  81. Byun HM, Benachour N, Zalko D, Frisardi MC, Colicino E, Takser L, et al. Epigenetic effects of low perinatal doses of flame retardant BDE-47 on mitochondrial and nuclear genes in rat offspring. Toxicology. 2015;328:152–9.

    Article  CAS  PubMed  Google Scholar 

  82. Liao K, Yan J, Mai K, Ai Q. Dietary olive and perilla oils affect liver mitochondrial DNA methylation in large yellow croakers. J Nutr. 2015;145(11):2479–85.

    Article  CAS  PubMed  Google Scholar 

  83. Ghosh S, Sengupta S, Scaria V. Comparative analysis of human mitochondrial methylomes shows distinct patterns of epigenetic regulation in mitochondria. Mitochondrion. 2014;18:58–62 .This study describes the first comprehensive map of mtDNA methylation across the human mitochondrial genome.

    Article  CAS  PubMed  Google Scholar 

  84. Gold DR, Mittleman MA. New insights into pollution and the cardiovascular system: 2010 to 2012. Circulation. 2013;127(18):1903–13.

    Article  PubMed  Google Scholar 

  85. Ge ZJ, Schatten H, Zhang CL, Sun QY. Oocyte ageing and epigenetics. Reproduction. 2015;149(3):R103–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Mitalipov S, Wolf DP. Clinical and ethical implications of mitochondrial gene transfer. Trends Endocrinol Metab. 2014;25(1):5–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ylikallio E, Suomalainen A. Mechanisms of mitochondrial diseases. Ann Med. 2012;44(1):41–59.

    Article  CAS  PubMed  Google Scholar 

  88. Edwards TM, Myers JP. Environmental exposures and gene regulation in disease etiology. Environ Health Perspect. 2007;115(9):1264–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Baccarelli AA, Byun HM. Platelet mitochondrial DNA methylation: a potential new marker of cardiovascular disease. Clin Epigenetics. 2015;7(1):44.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Yu Y, Su FC, Callaghan BC, Goutman SA, Batterman SA, Feldman EL. Environmental risk factors and amyotrophic lateral sclerosis (ALS): a case-control study of ALS in Michigan. PLoS One. 2014;9(6):e101186.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Wong M, Gertz B, Chestnut BA, Martin LJ. Mitochondrial DNMT3A and DNA methylation in skeletal muscle and CNS of transgenic mouse models of ALS. Front Cell Neurosci. 2013;7:279.

    PubMed  PubMed Central  Google Scholar 

  92. Smith CJ, Ryckman KK. Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome. Diabetes Metab Syndr Obes. 2015;8:295–302.

    PubMed  PubMed Central  Google Scholar 

  93. Zheng LD, Linarelli LE, Liu L, Wall SS, Greenawald MH, Seidel RW, et al. Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans. Clin Epigenetics. 2015;7(1):60.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Mishra M, Kowluru RA. Epigenetic modification of mitochondrial DNA in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2015;56(9):5133–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Weisenberger DJ, Levine AJ, Long TI, Buchanan DD, Walters R, Clendenning M, et al. Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history. Cancer Epidemiol Biomark Prev. 2015;24(3):512–9.

    Article  CAS  Google Scholar 

  96. Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, et al. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 2012;22(2):271–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Gao J, Wen S, Zhou H, Feng S. De-methylation of displacement loop of mitochondrial DNA is associated with increased mitochondrial copy number and nicotinamide adenine dinucleotide subunit 2 expression in colorectal cancer. Mol Med Rep. 2015;12(5):7033–8.

    CAS  PubMed  Google Scholar 

  98. Ahuja N, Easwaran H, Baylin SB. Harnessing the potential of epigenetic therapy to target solid tumors. J Clin Invest. 2014;124(1):56–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Cowan LA, Talwar S, Yang AS. Will DNA methylation inhibitors work in solid tumors? A review of the clinical experience with azacitidine and decitabine in solid tumors. Epigenomics. 2010;2(1):71–86.

    Article  CAS  PubMed  Google Scholar 

  100. Luck ME, Muljo SA, Collins CB. Prospects for therapeutic targeting of MicroRNAs in human immunological diseases. J Immunol. 2015;194(11):5047–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bollati V, Favero C, Albetti B, Tarantini L, Moroni A, Byun HM, et al. Nutrients intake is associated with DNA methylation of candidate inflammatory genes in a population of obese subjects. Nutrients. 2014;6(10):4625–39.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Hardy TM, Tollefsbol TO. Epigenetic diet: impact on the epigenome and cancer. Epigenomics. 2011;3(4):503–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. van der Wijst MG, Rots MG. Mitochondrial epigenetics: an overlooked layer of regulation? Trends Genet. 2015;31(7):353–6.

    Article  PubMed  Google Scholar 

  104. Pirola CJ, Gianotti TF, Burgueno AL, Rey-Funes M, Loidl CF, Mallardi P, et al. Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease. Gut. 2013;62(9):1356–63.

    Article  CAS  PubMed  Google Scholar 

  105. Jia Y, Li R, Cong R, Yang X, Sun Q, Parvizi N, et al. Maternal low-protein diet affects epigenetic regulation of hepatic mitochondrial DNA transcription in a sex-specific manner in newborn piglets associated with GR binding to its promoter. PLoS One. 2013;8(5):e63855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Luca Lambertini.

Ethics declarations

Conflict of Interest

Luca Lambertini and Hyang-Min Byun declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Environmental Epigenetics

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lambertini, L., Byun, HM. Mitochondrial Epigenetics and Environmental Exposure. Curr Envir Health Rpt 3, 214–224 (2016). https://doi.org/10.1007/s40572-016-0103-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40572-016-0103-2

Keywords

Navigation