Abstract
Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. 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.
Highlights
Mitochondria are double-membrane organelles which play a vital role in a variety of key biological functions, including production of ATP through oxidative phosphorylation (OXPHOS), apoptosis via caspase-dependent and independent mechanisms, regulation of calcium homeostasis and production of reactive oxygen species (ROS) [1]
The discovery of mitoepigenetic mechanisms has opened a new window of research that could provide new knowledge on the mitochondria regulation in both physiological and pathological conditions, with the potential to yield specific biomarkers for several human diseases
The literature reported in the current review indicates that mitoepigenetics has been poorly investigated compared to nuclear epigenetics in human diseases, it is clear that researchers are increasingly interested in this research field
Summary
Mitochondria are double-membrane organelles which play a vital role in a variety of key biological functions, including production of ATP through oxidative phosphorylation (OXPHOS), apoptosis via caspase-dependent and independent mechanisms, regulation of calcium homeostasis and production of reactive oxygen species (ROS) [1]. Mitochondria contain their own DNA, a molecule of 16,569 bp inherited in a maternal, non-Mendelian fashion. We discuss the possible impact of the nuclear genetic background and of environmental factors in the regulation of mtDNA methylation
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