Regulation of mitochondrial gene expression, the epigenetic enigma.

  title={Regulation of mitochondrial gene expression, the epigenetic enigma.},
  author={Archibold Mposhi and Monique G. P. van der Wijst and Klaas Nico Faber and Marianne G Rots},
  journal={Frontiers in bioscience},
Epigenetics provides an important layer of information on top of the DNA sequence and is essential for establishing gene expression profiles. Extensive studies have shown that nuclear DNA methylation and histone modifications influence nuclear gene expression. However, it remains unclear whether mitochondrial DNA (mtDNA) undergoes similar epigenetic changes to regulate mitochondrial gene expression. Recently, it has been shown that mtDNA is differentially methylated in various diseases such as… 

Figures and Tables from this paper

Mitochondrial DNA Methylation and Human Diseases

Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

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

This is the first study which directly addresses the potential functionality of mtDNA methylation and unravelling the impact of mt DNA methylation adds to the understanding of the role of mitochondria in physiological and pathophysiological processes.

Mitochondrial DNA: Epigenetics and environment

An overview of the epigenetic regulation of mtDNA via methylation, long and short noncoding RNAs, and post‐translational modifications of nucleoid proteins (as mitochondria lack histones) is provided.

Mitoepigenetics and Its Emerging Roles in Cancer

Modifications in mtDNA, mtRNA and nucleoids and modulations of mtDNA/nDNA-derived non-coding RNAs that affect mtDNA translation/function are summarized and recent studies of mitoepigenetic alterations in cancer are overviewed.

Mitochondrial Epigenetics Regulating Inflammation in Cancer and Aging

This review focuses on the intricate dynamics of epigenetic alterations of inflammation, with emphasis on mitochondria in cancer and aging.

The degree of mitochondrial DNA methylation in tumor models of glioblastoma and osteosarcoma

The findings highlight the influences that the nuclear and mitochondrial genomes have in setting mtDNA methylation patterns to regulate mtDNA copy number in tumorigenesis and the availability of mtDNA template for mtDNA replication.

Mitochondrial Epigenetics: Non-Coding RNAs as a Novel Layer of Complexity

This review presents the state-of-the-art knowledge about the mechanisms underlying mitoepigenetics and nuclei–mitochondria communication, and also about the involvement of the ncRNAs in mitochondrial functions and related diseases.



The Control Region of Mitochondrial DNA Shows an Unusual CpG and Non-CpG Methylation Pattern

The data show that DNA methylation occurs in the mtDNA control region of mammals, not only at symmetrical CpG dinucleotides, typical of nuclear genome, but in a peculiar non-CpG pattern previously reported for plants and fungi.

In vivo methylation of mtDNA reveals the dynamics of protein–mtDNA interactions

The studies focused on selected regions of mtDNA that are believed to be major regulatory regions involved in transcription and replication, and demonstrated that nucleoids are dynamically associated with proteins.

DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria

The presence of 5-hydroxymethylcytosine (5hmC) as well as 5mC in mammalian mtDNA is reported, suggesting that previous studies underestimated the level of cytosine modification in this genome.

Mitochondrial DNA: a blind spot in neuroepigenetics

Evidence supporting the existence of mitochondrial DNA methylation and hydroxymethylation is summarized for the first time and the term ‘mitochondrial epigenetics’ is proposed to be used when referring to them.

Epigenetic Modification of Mitochondrial DNA in the Development of Diabetic Retinopathy.

Hypermethylation of mtDNA in diabetes impairs its transcription, resulting in dysfunctional mitochondria and accelerated capillary cell apoptosis, and Regulation of mt DNA methylation has potential to restore mitochondrial homeostasis and inhibit/retard the development of diabetic retinopathy.

Platelet mitochondrial DNA methylation: a potential new marker of cardiovascular disease

The results suggest that platelet mtDNA methylation, which could serve as non-invasive and easy-to-obtain markers, may be implicated in the etiology of CVD.

Quantification of global mitochondrial DNA methylation levels and inverse correlation with age at two CpG sites

Regression analysis of methylation levels at two CpG sites located within the 12S ribosomal RNA gene showed an inverse correlation with subject age suggesting their utility as epigenetic markers of ageing.