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Is the mitochondrial cloud the selection machinery for preferentially transmitting wild-type mtDNA between generations? Rewinding Müller’s ratchet efficiently

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Abstract

In animal mitochondrial DNA inheritance, it remains largely unclear where the mitochondrial genetic bottleneck localizes and how it works in rewinding Müller’s ratchet. In a variety of different animals germ plasm mRNAs typically aggregate along with numerous mitochondria to form the mitochondrial cloud (MC) during oogenesis. The MC has been found to serve as messenger transport organizer for germ plasm mRNAs. Germ plasm RNAs in MC will specifically distribute to the primordial germ cells of the future embryo. It has been proposed that the MC might be the site where selected mitochondria accumulate for specific transmission to grandchildren but this idea received relatively little attention and the criterion by which mitochondria are selected remains unknown. Our recent results in zebrafish provided further evidence for selective mitochondria accumulation in the MC by showing that mitochondria with high-inner membrane potential tend to be recruited preferentially into the MC, and these mitochondria are transported along with germ plasm to the cortex of the vegetal pole. By analyzing the composition, behavior and functions of the MC, and in reviewing related literature, we found strong support for the proposition that the MC corresponds to the position and function of the mitochondrial genetic bottleneck.

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Fig. 1

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Abbreviations

MC:

Mitochondrial cloud

mtDNA:

Mitochondrial DNA

PGCs:

Primordial germ cells

METRO:

Messenger transport organizer

References

  • Amikura R, Sato K, Kobayashi S (2005) Role of mitochondrial ribosome-dependent translation in germline formation in Drosophila embryos. Mech Dev 122:1087–1093

    Article  CAS  PubMed  Google Scholar 

  • Ashley MV, Laipis PJ, Hauswirth WW (1989) Rapid segregation of heteroplasmic bovine mitochondria. Nucleic Acids Res 17:7325–7331

    Article  CAS  PubMed  Google Scholar 

  • Ballinger SW, Shoffner JM, Hedaya EV, Trounce I, Polak MA, Koontz DA, Wallace DC (1992) Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet 1:11–15

    Article  CAS  PubMed  Google Scholar 

  • Buszczak M, Cooley L (2000) Eggs to die for: cell death during Drosophila oogenesis. Cell Death Differ 7:1071–1074

    Article  CAS  PubMed  Google Scholar 

  • Cao L, Shitara H, Horii T, Nagao Y, Imai H, Abe K, Hara T, Hayashi J, Yonekawa H (2007) The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nat Genet 39:386–390

    Article  CAS  PubMed  Google Scholar 

  • Carelli V, Baracca A, Barogi S, Pallotti F, Valentino ML, Montagna P, Zeviani M, Pini A, Lenaz G, Baruzzi A, Solaini G (2002) Biochemical–clinical correlation in patients with different loads of the mitochondrial DNA T8993G mutation. Arch Neurol 59:264–270

    Article  PubMed  Google Scholar 

  • Chang P, Torres J, Lewis RA, Mowry KL, Houliston E, King ML (2004) Localization of RNAs to the mitochondrial cloud in Xenopus oocytes through entrapment and association with endoplasmic reticulum. Mol Biol Cell 15:4669–4681

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Prosser R, Simonetti S, Sadlock J, Jagiello G (1995) Rearranged mitochondrial genomes are present in human oocytes. Am J Hum Genet 57:239–247

    CAS  PubMed  Google Scholar 

  • Chinnery PF (2002) Inheritance of mitochondrial disorders. Mitochondrion 2:149–155

    Article  CAS  PubMed  Google Scholar 

  • Chinnery PF, Thorburn DR, Samuels DC, White SL, Dahl HHM, Turnbull DM, Lightowlers RN, Howell N (2000) The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both? Trends Genet 16:500–505

    Article  CAS  PubMed  Google Scholar 

  • Cox RT, Spradling AC (2003) A Balbiani body and the fusome mediate mitochondrial inheritance during Drosophila oogenesis. Development 130:1579–1590

    Article  CAS  PubMed  Google Scholar 

  • Cox RT, Spradling AC (2006) Milton controls the early acquisition of mitochondria by Drosophila oocytes. Development 133:3371–3377

    Article  CAS  PubMed  Google Scholar 

  • Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, Dahl HH, Chinnery PF (2008) A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet 40:249–254

    Article  CAS  PubMed  Google Scholar 

  • D’Herde K, Callebaut M, Roels F, De Prest B, van Nassauw L (1995) Homology between mitochondriogenesis in the avian and amphibian oocyte. Reprod Nutr Dev 35:305–311

    Article  PubMed  Google Scholar 

  • Fan W, Waymire KG, Narula N, Li P, Rocher C, Coskun PE, Vannan MA, Narula J, MacGregor GR, Wallace DC (2008) A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Science 319:958–962

    Article  CAS  PubMed  Google Scholar 

  • Felsenstein J (1974) The evolutionary advantage of recombination. Genetics 78:737–756

    CAS  PubMed  Google Scholar 

  • Hames RS, Hames R, Prosser SL, Euteneuer U, Lopes CA, Moore W, Woodland HR, Fry AM (2008) Pix1 and Pix2 are novel WD40 microtubule-associated proteins that colocalize with mitochondria in Xenopus germ plasm and centrosomes in human cells. Exp Cell Res 314:574–589

    Article  CAS  PubMed  Google Scholar 

  • Hauswirth WW, Laipis PJ (1982) Mitochondrial DNA polymorphism in a maternal lineage of Holstein cows. Proc Natl Acad Sci USA 79:4686–4690

    Article  CAS  PubMed  Google Scholar 

  • Iida T, Kobayashi S (1998) Essential role of mitochondrially encoded large rRNA for germ-line formation in Drosophila embryos. Proc Natl Acad Sci USA 95:11274–11278

    Article  CAS  PubMed  Google Scholar 

  • Inoue K, Nakada K, Ogura A, Isobe K, Goto Y, Nonaka I, Hayashi JI (2000) Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes. Nat Genet 26:176–181

    Article  CAS  PubMed  Google Scholar 

  • Jacobs H (2000) A mouse model of mtDNA disease. Trends Genet 16:487

    Article  PubMed  Google Scholar 

  • Jansen RPS, Burton GJ (2004) Mitochondrial dysfunction in reproduction. Mitochondrion 4:577–600

    Article  CAS  PubMed  Google Scholar 

  • Jansen RPS, de Boer K (1998) The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate. Mol Cell Endocrinol 145:81–88

    Article  CAS  PubMed  Google Scholar 

  • Jenuth JP, Peterson AC, Fu K, Shoubridge EA (1996) Random genetic drift in the female germ line explains the rapid segregation of mammalian mitochondrial DNA. Nat Genet 14:146–151

    Article  CAS  PubMed  Google Scholar 

  • Kashikawa M, Amikura R, Kobayashi S (2001) Mitochondrial small ribosomal RNA is a component of germinal granules in Xenopus embryos. Mech Dev 101:71–77

    Article  CAS  PubMed  Google Scholar 

  • Kloc M, Etkin LD (1998) Apparent continuity between the messenger transport organizer and late RNA localization pathways during oogenesis in Xenopus. Mech Dev 73:95–106

    Article  CAS  PubMed  Google Scholar 

  • Kloc M, Larabell C, Etkin LD (1996) Elaboration of the messenger transport organizer pathway for localization of RNA to the vegetal cortex of Xenopus oocytes. Dev Biol 180:119–130

    Article  CAS  PubMed  Google Scholar 

  • Kloc M, Bilinski S, Etkin LD (2004) The Balbiani body and germ cell determinants: 150 years later. Curr Top Dev Biol 59:1–36

    Article  CAS  PubMed  Google Scholar 

  • Kloc M, Shirato Y, Bilinski S, Browder LW, Johnston J (2007) Differential subcellular sequestration of proapoptotic and antiapoptotic proteins and colocalization of Bcl-xL with the germ plasm, in Xenopus laevis oocyte. Genesis 45:523–531

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi S, Okada M (1989) Restoration of pole-cell-forming ability to u.v. irradiated Drosophila embryos by injection of mitochondrial lrRNA. Development 107:733–742

    CAS  PubMed  Google Scholar 

  • Koehler CM, Lindberg GL, Brown DR, Beitz DC, Freeman AE, Mayfield JE, Myers AM (1991) Replacement of bovine mitochondrial DNA by a sequence variant within one generation. Genetics 129:247–255

    CAS  PubMed  Google Scholar 

  • Kosaka K, Kawakami K, Sakamoto H, Inoue K (2007) Spatiotemporal localization of germ plasm RNAs during zebrafish oogenesis. Mech Dev 124:279–289

    Article  CAS  PubMed  Google Scholar 

  • Laipis PJ, Van de Walle MJ, Hauswirth WW (1988) Unequal partitioning of bovine mitochondrial genotypes among siblings. Genetics 85:8107–8110

    CAS  Google Scholar 

  • Lane N (2008) Low variability on the W chromosome in birds is more likely to indicate selection on mitochondrial genes. Heredity 100:444–445

    Article  CAS  PubMed  Google Scholar 

  • Marchington DR, Macaulay V, Hartshorne GM, Barlow D, Poulton J (1998) Evidence from human oocytes for a genetic bottleneck in an mtDNA disease. Am J Hum Genet 63:769–775

    Article  CAS  PubMed  Google Scholar 

  • Martin Negrier ML, Coquet M, Moretto BT, Lacut JY, Dupon M, Bloch B, Lestienne P, Vital C (1998) Partial triplication of mtDNA in maternally transmitted diabetes mellitus and deafness. Am J Hum Genet 63:1227–1232

    Article  CAS  PubMed  Google Scholar 

  • Matova N, Cooley L (2001) Comparative aspects of animal oogenesis. Dev Biol 231:291–320

    Article  CAS  PubMed  Google Scholar 

  • Meirelles FV, Smith LC (1997) Mitochondrial genotype segregation in a mouse heteroplasmic lineage produced by embryonic karyoplast transplantation. Genetics 145:445–451

    CAS  PubMed  Google Scholar 

  • Nagley P, Wei YH (1998) Ageing and mammalian mitochondrial genetics. Trends Genet 14:513–517

    Article  CAS  PubMed  Google Scholar 

  • Olivo PD, Van de Walle MJ, Laipis PJ, Hauswirth WW (1983) Nucleotide sequence evidence for rapid genotypic shifts in the bovine mitochondrial DNA D-loop. Nature 306:400–402

    Article  CAS  PubMed  Google Scholar 

  • Pepling ME, Spradling AC (1998) Female mouse germ cells form synchronously dividing cysts. Development 125:3323–3328

    CAS  PubMed  Google Scholar 

  • Pepling ME, Spradling AC (2001) Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol 234:339–351

    Article  CAS  PubMed  Google Scholar 

  • Pepling ME, Wilhelm JE, O’Hara AL, Gephardt GW, Spradling AC (2007) Mouse oocytes within germ cell cysts and primordial follicles contain a Balbiani body. Proc Natl Acad Sci USA 104:187–192

    Article  CAS  PubMed  Google Scholar 

  • Poulton J, Holt I (1994) Mitochondrial DNA: does more lead to less? Nat Genet 8:313–315

    Article  CAS  PubMed  Google Scholar 

  • Saffman EE, Lasko P (1999) Germline development in vertebrates and invertebrates. Cell Mol Life Sci 55:1141–1163

    Article  CAS  PubMed  Google Scholar 

  • Sun QY, Wu GM, Lai L, Park KW, Gabot R, Cheong HT, Day BN, Prather RS, Schatten H (2001) Translocation of active mitochondria during pig oocyte maturation, fertilization and early embryo development in vitro. Reproduction 122:155–163

    Article  CAS  PubMed  Google Scholar 

  • Toivonen JM, O’Dell KM, Petit N, Irvine SC, Knight GK, Lehtonen M, Longmuir M, Luoto K, Touraille S, Wang Z, Alziari S, Shah ZH, Jacobs HT (2001) Technical knockout, a Drosophila model of mitochondrial deafness. Genetics 159:241–254

    CAS  PubMed  Google Scholar 

  • Van Blerkom J (2008) Mitochondria as regulatory forces in oocytes, preimplantation embryos and stem sells. Reprod Biomed Online 16:553–569

    Article  PubMed  Google Scholar 

  • Van Blerkom J, Davis P, Alexander S (2003) Inner mitochondrial membrane potential (ΔΨm), cytoplasmic ATP content and free Ca2+ levels in metaphase II mouse oocytes. Hum Reprod 18:2429–2440

    Article  PubMed  CAS  Google Scholar 

  • Viel A, Armand MJ, Callen JC, Gomez De Gracia A, Denis H, Ie Maire M (1990) Elongation factor 1 alpha (EF-1 alpha) is concentrated in the Balbiani body and accumulates coordinately with the ribosomes during oogenesis of Xenopus laevis. Dev Biol 141:270–278

    Article  CAS  PubMed  Google Scholar 

  • Wai T, Teoli D, Shoubridge EA (2008) The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes. Nat Genet 40:1488–14844

    Article  CAS  Google Scholar 

  • Wong LJ, Wong H, Liu A (2002) Intergenerational transmission of pathogenic heteroplasmic mitochondrial DNA. Genet Med 4:78–83

    Article  PubMed  Google Scholar 

  • Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF (2009) Inherited mitochondrial optic neuropathies. J Med Genet 46:145–158

    Article  CAS  PubMed  Google Scholar 

  • Zeviani M, Di Donato S (2004) Mitochondrial disorders. Brain 127:2153–2172

    Article  PubMed  Google Scholar 

  • Zhang YZ, Ouyang YC, Hou Y, Schatten H, Chen DY, Sun QY (2008) Mitochondrial behavior during oogenesis in zebrafish: a confocal microscopy analysis. Dev Growth Differ 50:189–201

    PubMed  Google Scholar 

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Acknowledgments

This work is supported by a grant from the Natural Science Foundation of Shandong, China (Y2007D06).

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Authors and Affiliations

  1. Department of Life Sciences, Liaocheng University, Liaocheng, 252059, Shandong, China

    Rong Rong Zhou, Bing Wang, Jing Wang & Yong Zhong Zhang

  2. Department of Veterinary Pathobiology, School of Veterinary Medicine, University of Missouri, 1600 E. Rollins Street, Columbia, MO, 65211, USA

    Heide Schatten

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  1. Rong Rong Zhou
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  2. Bing Wang
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  5. Yong Zhong Zhang
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Correspondence to Yong Zhong Zhang.

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Communicated by H. Jacobs.

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Zhou, R.R., Wang, B., Wang, J. et al. Is the mitochondrial cloud the selection machinery for preferentially transmitting wild-type mtDNA between generations? Rewinding Müller’s ratchet efficiently. Curr Genet 56, 101–107 (2010). https://doi.org/10.1007/s00294-010-0291-5

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