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山东大学学报 (医学版) ›› 2018, Vol. 56 ›› Issue (4): 23-27.doi: 10.6040/j.issn.1671-7554.0.2018.032

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线粒体异常与卵巢早衰

佟超   

  1. 浙江大学生命科学研究院, 浙江 杭州 310058
  • 发布日期:2022-09-27
  • 通讯作者: 佟超. E-mail:ctong@zju.edu.cn
  • 基金资助:
    国家重点研发计划(2017YFC1001100)

Mitochondrial defects and premature ovarian failure

TONG Chao   

  1. Life Sciences Institute, Zhejiang University, Hangzhou 310058, Zhejiang, China
  • Published:2022-09-27

摘要: 卵巢早衰是影响女性生殖健康的严重疾病,其致病机制尚不明确。线粒体作为细胞中重要的能量和代谢中心,参与细胞内多种生命活动,其功能异常与卵巢早衰密切相关。线粒体是哺乳动物细胞中惟一含有独立基因组的细胞器。在绝大多数动物中,线粒体DNA是母性遗传的,这意味着卵母细胞是线粒体将其遗传物质传递到下一代的惟一载体。卵母细胞体积大,线粒体DNA拷贝数多,线粒体形态也与体细胞有很大区别。这些特性使得卵巢中线粒体的功能及调控都有其特别之处。从线粒体DNA、线粒体蛋白合成与降解稳态,以及线粒体动态调节几个方面综述了线粒体异常与卵巢功能障碍和早衰的关系。

关键词: 线粒体, 卵巢早衰, 线粒体DNA, 线粒体动态, Perrault综合征

Abstract: Premature ovarian failure(POF)is a severe reproductive disease leading to infertility which affects many women. However, its etiology is not clear. Mitochondria, the energy factory and center of metabolism, participates many cellular activities. Malfunctions of mitochondria are associated with POF. Mitochondrion is the only organelle that has its own genome in the mammalian cells. In the majority of species, mitochondria are transmitted maternally, which means that oocyte is the only carrier that passes mitochondrial DNA(mtDNA)to the next generation. Oocytes are large and have many copies of mtDNA. The mitochondria in oocytes have distinct morphology compared with that in the 山 东 大 学 学 报 (医 学 版)56卷4期 -佟超.线粒体异常与卵巢早衰 \=-somatic cells. These special features of mitochondria in ovary lead to special regulatory mechanisms. In this review, we discussed how the defects in mtDNA, mitochondrial protein homeostasis, and mitochondrial dynamics lead to ovarian dysfunction.

Key words: Mitochondria, Premature ovarian failure, Mitochondrial DNA, Mitochondrial dynamics, Perrault syndrome

中图分类号: 

  • Q28
[1] López-Otín C, Galluzzi L, Freije JMP, et al. Metabolic control of longevity[J]. Cell, 2016, 166(4): 802-821.
[2] Laven JS. Primary ovarian insufficiency[J]. Semin Reprod Med, 2016, 34(4): 230-234.
[3] May-Panloup P, Boucret L, Chao de la Barca JM, et al. Ovarian ageing: the role of mitochondria in oocytes and follicles[J]. Hum Reprod Update, 2016, 22(6): 725-743.
[4] St John JC. Transmission, inheritance and replication of mitochondrial DNA in mammals: implications for reproductive processes and infertility[J]. Cell Tissue Res, 2012, 349(3): 795-808.
[5] Chen X, Prosser R, Simonetti S, et al. Rearranged mitochondrial genomes are present in human oocytes[J]. Am J Hum Genet, 1995, 57(2): 239-247.
[6] Reynier P, May-Panloup P, Chretien MF, et al. Mitochondrial DNA content affects the fertilizability of human oocytes[J]. Mol Hum Reprod, 2001, 7(5): 425-429.
[7] Spikings EC, Alderson J, St John JC. Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development[J]. Biol Reprod, 2007, 76(2): 327-335.
[8] May-Panloup P, Chretien MF, Jacques C, et al. Low oocyte mitochondrial DNA content in ovarian insufficiency[J]. Hum Reprod, 2005, 20(3): 593-597.
[9] Cao L, Shitara H, Horii T, et al. The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells[J]. Nat Genet, 2007, 39(3): 386-390.
[10] Cree LM, Samuels DC, de Sousa Lopes SC, et al. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes[J]. Nat Genet, 2008, 40(2): 249-254.
[11] Wai T, Teoli D, Shoubridge EA. The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes[J]. Nat Genet, 2008, 40(12): 1484-1488.
[12] Van Blerkom J. Mitochondria in human oogenesis and preimplantation embryogenesis: engines of metabolism, ionic regulation and developmental competence[J]. Reproduction, 2004, 128(3): 269-280.
[13] St John JC, Facucho-Oliveira J, Jiang Y, et al. Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells[J]. Hum Reprod Update, 2010, 16(5): 488-509.
[14] Diez-Juan A, Rubio C, Marin C, et al. Mitochondrial DNA content as a viability score in human euploid embryos: less is better[J]. Fertil Steril, 2015, 104(3): 534-541.
[15] Trifunovic A, Wredenberg A, Falkenberg M, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase[J]. Nature, 2004, 429(6990): 417-423.
[16] Luoma P, Melberg A, Rinne JO, et al. Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study[J]. Lancet, 2004, 364(9437): 875-882.
[17] Day FR, Ruth KS, Thompson DJ, et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1 -mediated DNA repair[J]. Nat Genet, 2015, 47(11): 1294-1303.
[18] Morino H, Pierce SB, Matsuda Y, et al. Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features[J]. Neurology, 2014, 83(22): 2054-2061.
[19] Demain LA, Urquhart JE, OSullivan J, et al. Expanding the genotypic spectrum of Perrault syndrome[J]. Clin Genet, 2017, 91(2): 302-312.
[20] Sissler M, Gonzalez-Serrano LE, Westhof E. Recent advances in mitochondrial aminoacyl-tRNA synthetases and disease[J]. Trends Mol Med, 2017, 23(8): 693-708.
[21] Pierce SB, Gersak K, Michaelson-Cohen R, et al. Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome[J]. Am J Hum Genet, 2013, 92(4): 614-620.
[22] Pierce SB, Chisholm KM, Lynch ED, et al. Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome[J]. Proc Natl Acad Sci U S A, 2011, 108(16): 6543-6548.
[23] Chatzispyrou IA, Alders M, Guerrero-Castillo S, et al. A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone, causes Perrault syndrome[J]. Hum Mol Genet, 2017, 26(13): 2541-2550.
[24] Jenkinson EM, Rehman AU, Walsh T, et al. Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease[J]. Am J Hum Genet, 2013, 92(4): 605-613.
[25] Haynes CM, Petrova K, Benedetti C, et al. ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans[J]. Dev Cell, 2007, 13(4): 467-480.
[26] Broadley SA, Hartl FU. Mitochondrial stress signaling: a pathway unfolds[J]. Trends Cell Biol, 2008, 18(1): 1-4.
[27] Gispert S, Parganlija D, Klinkenberg M, et al. Loss of mitochondrial peptidase Clpp leads to infertility, hearing loss plus growth retardation via accumulation of CLPX, mtDNA and inflammatory factors[J]. Hum Mol Genet, 2013, 22(24): 4871-4887.
[28] Youle RJ, van der Bliek AM, Mitochondrial fission, fusion, and stress[J]. Science, 2012, 337(6098): 1062-1065.
[29] Chan DC. Fusion and fission: interlinked processes critical for mitochondrial health[J]. Annu Rev Genet, 2012, 46: 265-287. doi: 10.1146/annurev-genet-110410-132529.
[30] Huang H, Gao Q, Peng X, et al. piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling[J]. Dev Cell, 2011, 20(3): 376-387.
[31] Zhang Y, Liu X, Bai J, et al. Mitoguardin regulates mitochondrial fusion through mitoPLD and is required for neuronal homeostasis[J]. Mol Cell, 2016, 61(1): 111-124.
[32] Motta PM, Nottola SA, Makabe S, et al. Mitochondrial morphology in human fetal and adult female germ cells[J]. Hum Reprod, 2000, 15(Suppl 2): 129-147.
[33] Sieber MH, Thomsen MB, Spradling AC. electron transport chain remodeling by GSK3 during oogenesis connects nutrient state to reproduction[J]. Cell, 2016, 164(3): 420-432.
[34] Dumollard R, Ward Z, Carroll J, et al. Regulation of redox metabolism in the mouse oocyte and embryo[J]. Development, 2007, 134(3): 455-465.
[35] Dumollard R, Duchen M, Carroll J. The role of mitochondrial function in the oocyte and embryo[J]. Curr Top Dev Biol, 2007, 77: 21-49. doi: 10.1016/S0070-2153(06)77002-8.
[36] Udagawa O, Ishihara T, Maeda M, et al. Mitochondrial fission factor Drp1 maintains oocyte quality via dynamic rearrangement of multiple organelles[J]. Curr Biol, 2014, 24(20): 2451-2458.
[37] Wakai T, Harada Y, Miyado K, et al. Mitochondrial dynamics controlled by mitofusins define organelle positioning and movement during mouse oocyte maturation[J]. Mol Hum Reprod, 2014, 20(11): 1090-1100.
[38] Liu XM, Zhang YP, Ji SY, et al. Mitoguardin-1 and -2 promote maturation and the developmental potential of mouse oocytes by maintaining mitochondrial dynamics and functions[J]. Oncotarget, 2016, 7(2): 1155-1167.
[39] Liu XM, Zhang YL, Ji SY, et al. Mitochondrial function regulated by Mitoguardin-1/2 is crucial for ovarian endocrine functions and ovulation[J]. Endocrinology, 2017, 158(11): 3988-3999.
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