Format

Send to

Choose Destination
Sci Rep. 2017 Mar 14;7(1):177. doi: 10.1038/s41598-017-00263-z.

Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression.

Author information

1
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Hanzeplein 1, 9713, GZ, Groningen, The Netherlands.
2
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Hanzeplein 1, 9713, GZ, Groningen, The Netherlands. m.g.rots@umcg.nl.

Abstract

Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the detection of mtDNA methylation as well as hydroxymethylation. Importantly, differential mtDNA methylation has been linked to aging and diseases, including cancer and diabetes. However, functionality of mtDNA methylation has not been demonstrated. Therefore, we targeted DNA methylating enzymes (modifying cytosine in the CpG or GpC context) to the mtDNA. Unexpectedly, mtDNA gene expression remained unchanged upon induction of CpG mtDNA methylation, whereas induction of C-methylation in the GpC context decreased mtDNA gene expression. Intriguingly, in the latter case, the three mtDNA promoters were differentially affected in each cell line, while cellular function seemed undisturbed. In conclusion, this is the first study which directly addresses the potential functionality of mtDNA methylation. Giving the important role of mitochondria in health and disease, unravelling the impact of mtDNA methylation adds to our understanding of the role of mitochondria in physiological and pathophysiological processes.

PMID:
28282966
PMCID:
PMC5428053
DOI:
10.1038/s41598-017-00263-z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center