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线粒体表观遗传修饰及药物靶点研究进展
线粒体表观遗传修饰及药物靶点研究进展
杨滢霖,李伟瀚,王月华,杜冠华

中国医学科学院药物研究所 药物靶点研究与新药筛选北京市重点实验室,北京 100050
Research progress of mitochondrial epigenetic modification and drug targets
(Beijing Key Laboratory of Drug Target Identification and New Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China)

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起始页:53

摘要:[摘要] 线粒体是细胞氧化磷酸化的场所,拥有自身的遗传物质和遗传体系,属于半自主细胞器。除为细胞供能外,还参与诸如细胞分化、细胞信息传递和细胞凋亡等生命过程,并拥有调控细胞生长的能力。线粒体DNA与核DNA类似,也存在表观遗传修饰,本文对线粒体表观遗传修饰研究进展进行文献综述,对基于线粒体表观遗传发现新颖药物靶点及生物标记物具有重要意义。

关键词:[关键词] 线粒体;表观遗传;甲基化;羟甲基化

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Abstract:[Abstract] Mitochondrion, an organelle of cell oxidative phosphorylation, possesses its own genetic materials and genetic systems, and is a kind of semi-autonomous organelle. In addition to providing energy for the cell, mitochondrion also participates in processes such as cell differentiation, cell information transfer, cell apoptosis, and cell growth regulation. At present, some data indicate that mitochondrial DNA belongs to epigenetic modification like nuclear DNA. In this paper, we reviewed the research on mitochondrial epigenetic modification in recent years. This modification is of great significance for the discovery of novel therapeutic targets and biomarkers based on mitochondrial epigenetic modification.

Key words:[Key words] mitochondria; epigenetic modification; methylation; hydroxymethylation

    [1] FELLING RJ, GUO JU, SONG H. Neuronal activation and insight into the plasticity of DNA methylation[J]. Epigenomics, 2012, 4(2): 125-127.
    [2] SUHM T, OTT M. Mitochondrial translation and cellular stress response[J]. Cell Tissue Res, 2017, 367(1): 21-31.
    [3] KOLESNIKOV AA. The mitochondrial genome[J]. The Nucleoid Biochemistry (Mosc), 2016, 81(10): 1057-1065.
    [4] D'AQUILA P, MONTESANTO A, GUARASCI F, et al. Mitochondrial genome and epigenome: two sides of the same coin[J]. Front Biosci (Landmark Ed), 2017, 22(1): 888-908.
    [5] INFANTINO V, CASTEGNA A, IACOBAZZI F, et al. Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome[J]. Mol Genet Metab, 2011, 102(3): 378-382.
    [6] SHOCK LS, THAKKAR PV, PETERSON EJ, et al. DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria[J]. Proc Natl Acad Sci USA, 2011, 108(9): 3630-3635.
    [7] GLUCKMAN PD, HANSON MA, BUKLIJAS T, et al. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases[J]. Nat Rev Endocrinol, 2009, 5(7): 401-408.
    [8] WALLACE DC, FAN W. Energetics, epigenetics, mitochondrial genetics[J]. Mitochondrion, 2010, 10(1): 12-31.
    [9] CHEN CC, WANG KY, SHEN CK. The mammalian de novo DNA methyltransferases DNMT3A and DNMT3B are also DNA 5-hydroxymethylcytosine dehydroxymethylases[J]. J Biol Chem, 2012, 287(40): 33116-33121.
    [10] GHOSH S, SENGUPTA S, SCARIA V. Hydroxymethyl cytosine marks in the human mitochondrial genome are dynamic in nature[J]. Mitochondrion, 2016, 27(2): 25-31.
    [11] BRANCO MR, FICZ G, REIK W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome[J]. Nat Rev Genet, 2011, 13(1): 7-13.
    [12] HE YF, LI BZ, LI Z, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA[J]. Science, 2011, 333(6047): 1303-1307.
    [13] SIEBER F, PLACIDO A, El FAROUK-AMEQRANE S, et al. A protein shuttle system to target RNA into mitochondria[J]. Nucleic Acids Res, 2011, 39(14): e96.
    [14] BAR-YAACOV D, BLUMBERG A, MISHMAR D. Mitochondrial-nuclear co-evolution and its effects on OXPHOS activity and regulation[J]. Biochim Biophys Acta, 2012, 1819(9-10): 1107-1111.
    [15] KELLY RD, MAHMUD A, MCKENZIE M, et al. Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A[J]. Nucleic Acids Res, 2012, 40(20): 10124-10138.
    [16] DUARTE FV, PALMERIA CM, ROLO AP. The emerging role of mito-miRs in the pathophysiology of human disease[J]. Adv Exp Med Biol, 2015, 888: 123-154.
    [17] CHEN Z, LI Y, ZHANG H, et al. Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression[J]. Oncogene, 2010, 29(30): 4362-4368.
    [18] LI J, DONATH S, LI Y, et al. miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway[J]. PLoS Genet, 2010, 6(1): e1000795.
    [19] SRIPADA L, SINGH K, LIPATOVA AV, et al. hsa-miR-4485 regulates mitochondrial functions and inhibits the tumorigenicity of breast cancer cells[J]. J Mol Med (Berl), 2017, 95(6):641-651.
    [20] SRIPADA L, TOMAR D, PRAJAPATI P, et al. Systematic analysis of small RNAs associated with human mitochondria by deep sequencing: detailed analysis of mitochondrial associated miRNA[J]. PLoS One, 2012, 7(9): e44873.
    [21] BELLIZZI D, D'AQUILA P, GIORDANO M, et al. Global DNA methylation levels are modulated by mitochondrial DNA variants[J]. Epigenomics, 2012, 4(1):17-27. 
    [22] BYUN HM, PANNI T, MOTTA V, et al. Effects of airborne pollutants on mitochondrial DNA methylation[J]. Part Fibre Toxicol, 2013,10:18.
    [23] CASTEGNA A, IACOBAZZI V, INFANTINO V. The mitochondrial side of epigenetics[J]. Physiol Genomics, 2015, 47(8): 299-307. 
    [24] INFANTINO V, CASTEGNA A, IACOBAZZI F, et al. Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome[J]. Mol Genet Metab, 2011, 102(3): 378-382.
    [25] CHESTNUT BA, CHANG Q, PRICE A, et al. Epigenetic regulation of motor neuron cell death through DNA methylation[J]. J Neurosci, 2011, 31(46): 16619-16636.
    [26] COSKUN P, WYREMBAK J, SCHRINER SE, et al. A mitochondrial etiology of Alzheimer and Parkinson disease[J]. Biochim Biophys Acta, 2012, 1820(5): 553-564.
    [27] CHEN H, DZITOYEVA S, MANEV H. Effect of valproic acid onmitochondrial epigenetics[J]. Eur J Pharmacol, 2012, 690(1-3):51-59.
    编辑:杨青/接受日期:2017-07-03