Table 5.

mtDNA methylation studies in other diseases.

Experimental Model	Method	mtDNA Region Investigated	Observation	Reference
Lymphoblastoid cells from 6 Down’s syndrome (DS) children and 6 control subjects	Mass spectrometry	Global mtDNA 5-mC content	mtDNA was hypomethylated in DS compared to healthy subjects	[102]
Liver biopsies from 22 patients with non-alcoholic steatohepatitis and 23 patients with simple steatosis	Methylation-specific PCR	D-loop region and MT-ND6 and MT-CO1 genes	Higher MT-ND6 methylation and lower MT-ND6 gene expression in individuals with simple steatosis. MT-ND6 methylation status inversely correlated with physical activity.	[103]
Fetal cord blood of newborns from mothers with placenta insufficiency and controls	Pyrosequencing	D-loop region and MT-RNR1 and MT-CO1 genes	Decreased D-loop methylation levels in cases compared to controls. D-loop methylation levels were associated with poorer fetal outcomes. Inverse correlation between MT-CO1 methylation levels and mtDNA content.	[104]
Peripheral blood of 118 patients with major depressive disorder (MDD) and 116 control subjects	Methylation-specific PCR	D-loop region and nuclear PGC1α gene promoter	Patients with MDD had a higher mtDNA copy number and decreased DNA methylation in the PGC1α gene promoter. D-loop methylation levels did not differ between MDD and control subjects.	[105]
Peripheral blood cells from 70 ADHD subjects and 70 healthy controls	Methylation-specific PCR	D-loop region and nuclear PPARGC1A gene	mtDNA copy number was significantly higher in ADHD patients than in controls. Methylation levels of PPARGC1A were decreased in ADHD patients compared to controls. D-loop methylation levels did not differ between ADHD and control subjects.	[106]