Global DNA Methylation Levels are Modulated by Mitochondrial DNA Variants

Abstract

Aim: In the present study, we investigated whether global DNA methylation levels are affected by mitochondrial DNA (mtDNA) variants, which are known to modulate mitochondrial functions. Materials & methods: Global DNA methylation levels were evaluated in peripheral blood DNA collected from adult subjects and in vitro using the DNA of cybrid cells harboring mtDNAs of different haplogroups. In these cells, mRNA expression of genes involved in DNA methylation processes, and ATP and reactive oxygen species levels were also analyzed. Results: The analysis revealed that methylation levels were higher in the subjects carrying the J haplogroup than in non-J carriers. Consistently, cybrids with J haplogroup mtDNA showed higher methylation levels than other cybrids. Interestingly, we observed overexpression of the MAT1A gene and low ATP and ROS levels in J cybrids. Conclusion: Our findings indicate that mtDNA-specific interactions between mitochondria and the nucleus regulate epigenetic changes, possibly by affecting oxidative phosphorylation efficiency.

KEYWORDS::

• ATP
• cybrid cell lines
• global DNA methylation
• MAT1A gene
• mitochondrial DNA variability
• ROS

Financial & competing interests disclosure

The research leading to these results has received funding from the European Union‘s Seventh Framework Programme (FP7/2007-2011) under grant agreement n 259679 and from ‘Fondi di Ateneo‘ of the University of Calabria. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The research leading to these results has received funding from the European Union‘s Seventh Framework Programme (FP7/2007-2011) under grant agreement n 259679 and from ‘Fondi di Ateneo‘ of the University of Calabria. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.