title: Global DNA methylation levels are modulated by mitochondrial DNA variants.
abstract: OBJECTIVE
  In the present study, we investigated whether global DNA methylation levels are affected by mitochondrial DNA (mtDNA) variants, which are known to modulate mitochondrial functions.
  
  
  METHODS
  Global DNA methylation levels were evaluated in peripheral blood DNA collected from adult subjects and in vitro using the DNA of cybrid cells harboring mtDNAs of different haplogroups. In these cells, mRNA expression of genes involved in DNA methylation processes, and ATP and reactive oxygen species levels were also analyzed.
  
  
  RESULTS
  The analysis revealed that methylation levels were higher in the subjects carrying the J haplogroup than in non-J carriers. Consistently, cybrids with J haplogroup mtDNA showed higher methylation levels than other cybrids. Interestingly, we observed overexpression of the MAT1A gene and low ATP and ROS levels in J cybrids.
  
  
  CONCLUSIONS
  Our findings indicate that mtDNA-specific interactions between mitochondria and the nucleus regulate epigenetic changes, possibly by affecting oxidative phosphorylation efficiency.
authors.affiliation: Department of Cell Biology, University of Calabria, 87036 Rende, Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Bellizzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Aquila
authors.forename: Marco
authors.initials: M
authors.lastname: Giordano
authors.forename: Alberto
authors.initials: A
authors.lastname: Montesanto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008716:Methionine Adenosyltransferase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C506577:MAT1A protein, human; D008716:Methionine Adenosyltransferase