z-logo
Premium
The control of mitochondrial DNA replication during development and tumorigenesis
Author(s) -
Lee William T.Y.,
John Justin St.
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12873
Subject(s) - mitochondrial dna , biology , carcinogenesis , induced pluripotent stem cell , dna methylation , stem cell , microbiology and biotechnology , cancer cell , genetics , cancer , embryonic stem cell , gene , gene expression
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.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here