Mitochondrial DNA Methylation as a Next-Generation Biomarker and Diagnostic Tool

Mol Genet Metab. Sep-Oct 2013;110(1-2):25-34. doi: 10.1016/j.ymgme.2013.07.012. Epub 2013 Jul 19.


Recent expansion of our knowledge on epigenetic changes strongly suggests that not only nuclear DNA (nDNA), but also mitochondrial DNA (mtDNA) may be subjected to epigenetic modifications related to disease development, environmental exposure, drug treatment and aging. Thus, mtDNA methylation is attracting increasing attention as a potential biomarker for the detection and diagnosis of diseases and the understanding of cellular behavior in particular conditions. In this paper we review the current advances in mtDNA methylation studies with particular attention to the evidences of mtDNA methylation changes in diseases and physiological conditions so far investigated. Technological advances for the analysis of epigenetic variations are promising tools to provide insights into methylation of mtDNA with similar resolution levels as those reached for nDNA. However, many aspects related to mtDNA methylation are still unclear. More studies are needed to understand whether and how changes in mtDNA methylation patterns, global and gene specific, are associated to diseases or risk factors.

Keywords: 5-MTHF; 5-hydroxymethylcytosine; 5-methyl-tetrahydrofolate; 5-methylcytosine; 5hmC; 5mC; AD; AIMs; ALS; Alzheimer disease; Biomarker; CBS; CHARM; CTH; ChIP; DNA methyltransferase; DNMT; DS; Down's syndrome; Epigenetics; Hcy; MAT; MBE; MCA; MMAss; MS; MT; MTHFR; MeDIP and mDIP; Methylation; Mitochondrial DNA; Ms-AP-PCR; MsCC; NAFLD; NASH; PD; Parkinson disease; ROS; S-adenosylhomocysteine; S-adenosylmethionine; SAH; SAH hydrolase; SAHH; SAM; SHMT; TET; TFA; TFB; THF; WGsBs; amplification of inter-methylated sites; amyotrophic lateral sclerosis; chromatin immunoprecipitation; comprehensive high-throughput arrays for relative methylation; cystathionine β-synthase; cystathionine γ-lyase; homocysteine; methionine adenosyltransferase; methionine synthase; methylated CpG island amplification; methylated DNA immunoprecipitation; methylation-sensitive arbitrarily primed PCR; methylation-sensitive cut counting; methylenetetrahydrofolate reductase; methyltransferase; microarray-based methylation assessment of single samples; mitochondrial DNA; mitochondrial bifunctional enzyme; mtDNA; nDNA; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; nuclear DNA; reactive oxygen species; serine hydroxymethyltransferase; ten–eleven translocation; tetrahydrofolate; transcription factor A; transcription factor B; whole-genome shotgun bisulfite sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers*
  • DNA Methylation / genetics*
  • DNA, Mitochondrial / genetics*
  • Epigenesis, Genetic*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • S-Adenosylhomocysteine


  • Biomarkers
  • DNA, Mitochondrial
  • S-Adenosylhomocysteine