Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119591
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Type: Journal article
Title: The control of mitochondrial DNA replication during development and tumorigenesis
Author: Lee, W.
John, J.
Citation: Annals of the New York Academy of Sciences, 2015; 1350(1):95-106
Publisher: New York Academy of Sciences
Issue Date: 2015
ISSN: 0077-8923
1749-6632
Statement of
Responsibility: 
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 methylation of POLGA is instrumental in the fate of pluripotent stem cells and cancer cells.
Keywords: Mitochondrial DNA; mtDNA; POLGA; pluripotency; differentiation; mtDNA set point; tumorigenesis
Rights: © 2015 New York Academy of Sciences.
RMID: 0030112568
DOI: 10.1111/nyas.12873
Grant ID: http://purl.org/au-research/grants/nhmrc/1041471
Appears in Collections:Medicine publications

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