Mitochondrial DNA Methylation and Human Diseases.
Andrea StoccoroFabio CoppedèPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- dna methylation
- genome wide
- copy number
- mitochondrial dna
- endothelial cells
- gene expression
- oxidative stress
- induced pluripotent stem cells
- type diabetes
- cardiovascular disease
- pluripotent stem cells
- metabolic syndrome
- insulin resistance
- prognostic factors
- squamous cell carcinoma
- adipose tissue
- body mass index
- ejection fraction
- weight gain
- newly diagnosed
- cell death
- weight loss
- circulating tumor
- transcription factor
- physical activity
- skeletal muscle