The control of mitochondrial DNA replication during development and tumorigenesis

Annals of the New York Academy of Sciences
William T Y Lee, Justin St John

Abstract

Mitochondrial DNA (mtDNA) copy number is strictly regulated during development and tumorigenesis. Pluripotent stem cells and cancer stem-like cells use glycolysis for energy metabolism, as they possess low mtDNA copy number, which promotes cell proliferation. As pluripotent stem cells can differentiate into all cell types of the body, they establish the mtDNA set point during early development, maintaining mtDNA copy number at low levels but enabling differentiating cells to acquire the appropriate numbers of mtDNA copy to meet their specific demands for OXPHOS-derived ATP, as they become specialized cells. This process is mediated by changes to DNA methylation at exon 2 of the catalytic subunit of the mitochondrial-specific polymerase, POLGA. Cancer stem-like cells, however, are hypermethylated and maintain low mtDNA copy number, resulting in their dependence on aerobic glycolysis. Their hypermethylation at exon 2 of POLGA also promotes their multipotent state. As a result, cancer cells are unable to increase their mtDNA content and differentiate into specific lineages unless they are treated with DNA demethylation agents or partially depleted of their mtDNA. This review describes these processes in depth and argues that DNA m...Continue Reading

References

Apr 1, 1982·Cell·D A Clayton
Aug 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·W W Hauswirth, P J Laipis
Sep 1, 1984·Experimental Cell Research·N B Hecht, H Liem
Apr 9, 1981·Nature·S AndersonI G Young
Aug 2, 1996·Cancer Letters·B C Liang, L Hays
Jan 1, 1996·Methods in Enzymology·G S Shadel, D A Clayton
Oct 6, 1999·Current Opinion in Microbiology·S G Andersson, C G Kurland
Dec 10, 1999·Nature·P SutovskyG Schatten
Oct 21, 2000·Human Reproduction·D A Clayton
Oct 21, 2000·Human Reproduction·E A Shoubridge
Nov 14, 2000·Trends in Genetics : TIG·P F ChinneryN Howell
May 2, 2001·Molecular Human Reproduction·P ReynierY Malthièry
Jul 31, 2001·International Journal of Cancer. Journal International Du Cancer·E KirchesK Dietzmann
Aug 23, 2002·The New England Journal of Medicine·Marianne Schwartz, John Vissing
Jan 7, 2003·Genes & Development·Ariel A AvilionRobin Lovell-Badge
Mar 5, 2003·Human Reproduction·P May-PanloupP Reynier
Jul 9, 2004·Fertility and Sterility·Shu-Huei KaoYau-Huei Wei
Sep 21, 2004·Oncogene·Ian Chambers, Austin Smith
Oct 30, 2004·Reproductive Biomedicine Online·Josie M L McConnell, Linda Petrie
May 13, 2005·Human Molecular Genetics·Nicole HanceAleksandra Trifunovic
May 14, 2005·Genes, Chromosomes & Cancer·Chew-Wun WuHsin-Chen Lee
May 17, 2005·Molecular Reproduction and Development·Jacob ThundathilLawrence C Smith
Jun 21, 2005·Annals of the New York Academy of Sciences·Hsin-Chen LeeYau-Huei Wei
Jul 25, 2006·Current Biology : CB·Heidi M McBrideSylwia Wasiak
Jan 16, 2007·Current Topics in Developmental Biology·Eric A Shoubridge, Timothy Wai
Apr 6, 2007·Annual Review of Biochemistry·Maria FalkenbergClaes M Gustafsson
Nov 1, 2007·Journal of Cell Science·Joao M Facucho-OliveiraJustin C St John
Jun 14, 2008·Current Protocols in Nucleic Acid Chemistry·Hikoya HayatsuKazuo Negishi
Dec 4, 2008·British Journal of Cancer·E WebbR S Houlston

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Citations

May 26, 2016·Breast Cancer Research : BCR·Maria Peiris-PagèsMichael P Lisanti
May 25, 2016·Molecular and Cellular Biology·Caitlyn E BowmanMichael J Wolfgang
Jul 6, 2018·Cellular and Molecular Life Sciences : CMLS·Zijun WangQianjin Lu
Feb 11, 2020·Frontiers in Cell and Developmental Biology·Zhen DongHongjuan Cui
Feb 14, 2021·Cellular and Molecular Life Sciences : CMLS·Dane T Sessions, David F Kashatus

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