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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.