Mitochondrial DNA replication is critical for maintaining mtDNA copy number to generate sufficient cellular energy that is required for development and for functional cells. In early development, mtDNA copy number is strictly regulated at different stages, and, as a result, the establishment of the mtDNA set point is required for sequential cell lineage commitment. The failure to establish the mtDNA set point results in incomplete differentiation or embryonic arrest. The regulation of mtDNA copy number during differentiation is closely associated with cellular gene expression, especially with the pluripotency network, and DNA methylation profiles. The findings from cancer research highlight the relationship between mitochondrial function, mtDNA copy number and DNA methylation in regulating differentiation. DNA methylation at exon 2 of DNA polymerase gamma subunit A (POLGA) has been shown to be a key factor, which can be modulated to change the mtDNA copy number and cell fate of differentiating and tumour cells. The present review combines multi-disciplinary data from mitochondria, development, epigenetics and tumorigenesis, which could provide novel insights for further research, especially for developmental disorders and cancers.
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October 2016
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Cover Image
Cover Image
Crystal structure of human hemoglobin β subunit (PDB ID: 1A3N) with an in silico mutation of phenylalanine 41 to tyrosine (green) to enhance function as a blood substitute; image kindly provide by Brandon Reeder and Chris Cooper (University of Essex). For details see Silkstone et al. in this issue (pages 3371–3383).
Review Article|
September 27 2016
The role of the mtDNA set point in differentiation, development and tumorigenesis
Xin Sun;
Xin Sun
1Centre for Genetic Diseases, Hudson Institute of Medical Research, 27–31 Wright Street, Clayton, VIC 3168, Australia
2Department of Molecular and Translational Sciences, Monash University, 27–31 Wright Street, Clayton, VIC 3168, Australia
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Justin C. St. John
Justin C. St. John
1Centre for Genetic Diseases, Hudson Institute of Medical Research, 27–31 Wright Street, Clayton, VIC 3168, Australia
2Department of Molecular and Translational Sciences, Monash University, 27–31 Wright Street, Clayton, VIC 3168, Australia
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Publisher: Portland Press Ltd
Received:
January 22 2016
Revision Received:
May 17 2016
Accepted:
June 06 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem J (2016) 473 (19): 2955–2971.
Article history
Received:
January 22 2016
Revision Received:
May 17 2016
Accepted:
June 06 2016
Citation
Xin Sun, Justin C. St. John; The role of the mtDNA set point in differentiation, development and tumorigenesis. Biochem J 1 October 2016; 473 (19): 2955–2971. doi: https://doi.org/10.1042/BCJ20160008
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