Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

The mitochondrial contribution to stem cell biology

Barry D. Bavister
+ Author Affiliations
- Author Affiliations

Department of Biological Sciences, University of New Orleans, 200 Computer Center, New Orleans, LA 70148-2960, USA. Email: bbaviste@uno.edu

Reproduction, Fertility and Development 18(8) 829-838 https://doi.org/10.1071/RD06111
Submitted: 8 June 2006  Accepted: 4 September 2006   Published: 22 November 2006

Abstract

The distribution and functions of mitochondria in stem cells have not been examined, yet the contributions of these organelles to stem cell viability and differentiation must be vitally important in view of their critical roles in all other cell types. A key role for mitochondria in stem cells is indicated by reports that they translocate in the oocyte during fertilisation to cluster around the pronuclei and can remain in a perinuclear pattern during embryo development. This clustering appears to be essential for normal embryonic development. Because embryonic stem cells are derived from fertilised oocytes, and eventually can differentiate into ‘adult’ stem cells, it was hypothesised that mitochondrial perinuclear clustering persists through preimplantation embryo development into the stem cells, and that this localisation is indicative of stem cell pluripotency. Further, it was predicted that mitochondrial activity, as measured by respiration and adenosine triphosphate (ATP) content, would correlate with the degree of perinuclear clustering. It was also predicted that these morphological and metabolic measurements could serve as indicators of ‘stemness.’ This article reviews the distribution and metabolism of mitochondria in a model stem cell line and how this information is related to passage number, differentiation and/or senescence. In addition, it describes mitochondrial DNA deletions in oocytes and embryos that could adversely affect stem cell performance.

Extra keywords: adipose stem cells, differentiation, metabolism, mitochondrial localisation, rhesus monkey, senescence.


Acknowledgments

I want to acknowledge my colleagues: Dr Tom Lonergan who conducted the functional analyses of mitochondria in stem cells; Dr Carol Brenner and Tiffini Gibson who did the mitochondrial molecular analyses of monkey oocytes; Drs Don Wolf and Shoukhrat Mitalipov from the Oregon National Primate Center for supplying ES cell lines, which gave our laboratory a huge boost and which are especially appreciated in the aftermath of hurricane Katrina, because we lost almost everything; Drs Bruce Bonnell and Michael Kubisch at the Tulane National Primate Research Center for supplying the monkey ATSC cell line and the testicular fibroblasts. Lastly but most importantly, I am grateful to the NIH for supporting our research studies (grant nos RR15395, RR021881 and HD045966).


References

Barnett, D. K. , Kimura, J. , and Bavister, B. D. (1996). Translocation of active mitochondria during hamster preimplantation embryo development studied by confocal laser scanning microscopy. Dev. Dyn. 205, 64–72.
CrossRef | PubMed |

Barnett, D. K. , Clayton, M. K. , Kimura, J. , and Bavister, B. D. (1997). Glucose and phosphate toxicity in hamster preimplantation embryos involves disruption of cellular organization, including distribution of active mitochondria. Mol. Reprod. Dev. 48, 227–237.
CrossRef | PubMed |

Barritt, J. A. , Brenner, C. A. , Cohen, J. , and Matt, D. W. (1999). Mitochondrial DNA rearrangements in human oocytes and embryos. Mol. Hum. Reprod. 5, 927–933.
CrossRef | PubMed |

Barritt, J. A. , Cohen, J. , and Brenner, C. A. (2000). Mitochondrial DNA point mutation in human oocytes is associated with maternal age. Reprod. Biomed. Online 1, 96–100.
PubMed |

Bavister, B. D. (2004). The role of animal studies in supporting human assisted reproductive technology. Reprod. Fertil. Dev. 16, 719–728.
PubMed |

Bavister, B. D. , and Brenner, C. A. (2004). How can basic science help human ART? The Clin. Embryologist 7, 6–11.


Bavister, B. D. , Wolf, D. P. , and Brenner, C. A. (2005). Challenges of primate embryonic stem cell research. Cloning Stem Cells 7, 82–94.
CrossRef | PubMed |

Birch-Machin, M. A. (2006). The role of mitochondria in ageing and carcinogenesis. Clin. Exp. Dermatol. 31, 548–552.
CrossRef | PubMed |

Brenner, C. A. , Wolny, Y. M. , Barritt, J. A. , Matt, D. W. , Munne, S. , and Cohen, J. (1998). Mitochondrial DNA deletion in human oocytes and embryos. Mol. Hum. Reprod. 4, 887–892.
CrossRef | PubMed |

Centers for Disease Control 2003. ‘2003 Assisted Reproductive Technology (ART) Report: Introduction to Fertility Clinic Tables.’ Available at http://www.cdc.gov/ART/ART2003/ifct.htm [Verified 1 June 2006].

Chinnery, P. F. , Samuels, D. C. , Elson, J. , and Turnbull, D. M. (2002). Accumulation of mitochondrial DNA mutations in ageing, cancer and mitochondrial disease: is there a common mechanism? Lancet 360, 1323–1325.
CrossRef | PubMed |

Collins, T. J. , Berridge, M. J. , Lipp, P. , and Bootman, M. D. (2002). Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J. 21, 1616–1627.
CrossRef | PubMed |

Cowan, C. A. , Klimanskaya, I. , McMahon, J. , Atienza, J. , and Witmyer, J. , et al. (2004). Derivation of embryonic stem-cell lines from human blastocysts. N. Engl. J. Med. 350, 1353–1356.
CrossRef | PubMed |

Draper, J. S. , Smith, K. , Gokhale, P. , Moore, H. D. , Maltby, E. , Johnson, J. , Meisner, L. , Zwaka, T. P. , Thomson, J. A. , and Andrews, P. W. (2004a). Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat. Biotechnol. 22, 53–54.
CrossRef | PubMed |

Draper, J. S. , Moore, H. D. , Ruban, L. N. , Gokhale, P. J. , and Andrews, P. W. (2004b). Culture and characterization of human embryonic stem cells. Stem Cells Dev. 13, 325–336.
CrossRef | PubMed |

Eichenlaub-Ritter, U. , Vogt, E. , Yin, H. , and Gosden, R. (2004). Spindles, mitochondria and redox potential in ageing oocytes. Reprod. Biomed. Online 8, 45–58.
PubMed |

Flores, I. , Cayuela, M. L. , and Blasco, M. A. (2005). Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309, 1253–1256.
CrossRef | PubMed |

Gaspari, M. , Larsson, N. G. , and Gustafsson, C. M. (2004). The transcription machinery in mammalian mitochondria. Biochim. Biophys. Acta 1659, 148–152.
CrossRef | PubMed |

Gibson, T. C. , Kubisch, H. M. , and Brenner, C. A. (2005). Mitochondrial DNA deletions in rhesus macaque oocytes and embryos. Mol. Hum. Reprod. 11, 785–789.
CrossRef | PubMed |

Gibson, T. C. , Pei, Y. , Quebedeaux, T. M. , and Brenner, C. A. (2006). Mitochondrial DNA deletions in primate embryonic and adult stem cells. Reprod. Biomed. Online 12, 101–106.
PubMed |

Hovatta, O. (2006). Derivation of human embryonic stem cell lines, towards clinical quality. Reprod. Fertil. Dev. 18, 823–828.
CrossRef |

Johnson, P. R. , Dolman, N. J. , Vaillant, C. , Petersen, O. H. , Tepkin, A. V. , and Erdemli, G. (2003). Non-uniform distribution of mitochondria in pancreatic acinar cells. Cell Tissue Res. 313, 37–45.
CrossRef | PubMed |

Kang, S. K. , Putnam, L. , Dufour, J. , Ylostalo, J. , Jung, J. S. , and Bunnell, B. A. (2004). Expression of telomerase extends the lifespan and enhances osteogenic differentiation of adipose tissue-derived stromal cells. Stem Cells 22, 1356–1374.
CrossRef | PubMed |

Keefe, D. L. , Niven-Fairchild, T. , Powell, S. , and Buradagunta, S. (1995). Mitochondrial deoxyribonucleic acid deletions in oocytes and reproductive aging in women. Fertil. Steril. 64, 577–583.
PubMed |

Kido, T. , Sekitani, T. , Okami, K. , Endo, S. , and Moriya, K. (1993). Ultrastructure of the chick vestibular ganglion and vestibular nucleus. A scanning electron microscopic study. Acta Otolaryngol. Suppl. 503, 161–165.
PubMed |

Lester, L. B. , Kuo, H. C. , Andrews, L. , Nauert, B. , and Wolf, D. P. (2004). Directed differentiation of rhesus monkey ES cells into pancreatic cell phenotypes. Reprod. Biol. Endocrinol. 2, 42..
CrossRef | PubMed |

Liu, L. , Hammar, K. , Smith, P. J. , Inoue, S. , and Keefe, D. L. (2001). Mitochondrial modulation of calcium signaling at the initiation of development. Cell Calcium 30, 423–433.
CrossRef | PubMed |

Lonergan, T. , Brenner, C. A. , and Bavister, B. D. (2006). Differentiation-related changes in mitochondrial properties as indicators of stem cell competence. J. Cell. Physiol. 208, 149–153.
CrossRef | PubMed |

Ludwig, T. E. , Squirrell, J. M. , Palmenberg, A. C. , and Bavister, B. D. (2001). Relationship between development, metabolism and mitochondrial organization in 2-cell hamster embryos in the presence of low levels of phosphate. Biol. Reprod. 65, 1648–1654.
CrossRef | PubMed |

McConnell, J. M. , and Petrie, L. (2004). Mitochondrial DNA turnover occurs during preimplantation development and can be modulated by environmental factors. Reprod. Biomed. Online 9, 418–424.
PubMed |

McKiernan, S. H. , and Bavister, B. D. (1998). Gonadotropin stimulation of donor females decreases post-implantation viability of cultured 1-cell hamster embryos. Hum. Reprod. 13, 724–729.
CrossRef | PubMed |

Park, M. K. , Ashby, M. C. , Erdemil, G. , Petersen, O. H. , and Tepikin, A. V. (2001). Perinuclear, perigranular and sub-plasmalemmal mitochondria have distinct functions in the regulation of cellular calcium transport. EMBO J. 20, 1863–1874.
CrossRef | PubMed |

Pau, K. Y. , and Wolf, D. P. (2004). Derivation and characterization of monkey embryonic stem cells. Reprod. Biol. Endocrinol. 2, 41..
CrossRef | PubMed |

Rossant, J. (2001). Stem cells from the mammalian blastocyst. Stem Cells 19, 477–482.
CrossRef | PubMed |

Schwarze, S. R. , Lee, C. M. , Chung, S. S. , Roecker, E. B. , Weindruch, R. , and Aiken, J. M. (1995). High levels of mitochondrial DNA deletions in skeletal muscle of old rhesus monkeys. Mech. Ageing Dev. 83, 91–101.
CrossRef | PubMed |

Singh, K. K. (2006). Mitochondria damage checkpoint, aging, and cancer. Ann. N. Y. Acad. Sci. 1067, 182–190.
CrossRef | PubMed |

Squirrell, J. M. , Lane, M. , and Bavister, B. D. (2001). Altering intracellular pH disrupts development and cellular organization in preimplantation hamster embryos. Biol. Reprod. 64, 1845–1854.
CrossRef | PubMed |

Squirrell, J. M. , Schramm, R. D. , Paprocki, A. M. , Wokosin, D. L. , and Bavister, B. D. (2003). Imaging mitochondrial organization in living primate oocytes and embryos using multiphoton microscopy. Microsc. Microanal. 9, 190–201.
CrossRef | PubMed |

van Blerkom, J. , Davis, P. W. , and Lee, J. (1995). ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer. Hum. Reprod. 10, 415–424.
PubMed |

van Blerkom, J. , Davis, P. , and Alexander, S. (2000). Differential mitochondrial distribution in human pronuclear embryos leads to disproportionate inheritance between blastomeres: relationship to microtubular organization, ATP content and competence. Hum. Reprod. 15, 2621–2633.
CrossRef | PubMed |

Vankoningsloo, S. , Piens, M. , Lecocq, C. , Gilson, A. , DePauw, A. , Renard, P. , Demazy, C. , Houbion, A. , Raes, M. , and Arnould, T. (2005). Mitochondrial dysfunction induces triglyceride accumulation in 3T3–L1 cells: role of fatty acid beta-oxidation and glucose. J. Lipid Res. 46, 1133–1149.
CrossRef | PubMed |

Wallace, D. (1993). Mitochondrial diseases: genotype versus phenotype. Trends Genet. 9, 128–133.
CrossRef | PubMed |

Yaffe, M. P. (1999). The machinery of mitochondrial inheritance and behavior. Science 283, 1493–1497.
CrossRef | PubMed |



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