49 Citations (Scopus)

Abstract

Epigenetics provides an important layer of information on top of the DNA sequence and is essential for establishing gene expression profiles. Extensive studies have shown that nuclear DNA methylation and histone modifications influence nuclear gene expression. However, it remains unclear whether mitochondrial DNA (mtDNA) undergoes similar epigenetic changes to regulate mitochondrial gene expression. Recently, it has been shown that mtDNA is differentially methylated in various diseases such as diabetes and colorectal cancer. Interestingly, this differential methylation was often associated with altered mitochondrial gene expression. However, the direct role of mtDNA methylation on gene expression remains elusive. Alternatively, the activity of the mitochondrial transcription factor A (TFAM), a protein involved in mtDNA packaging, might also influence gene expression. This review discusses the role of mtDNA methylation and potential epigeneticlike modifications of TFAM with respect to mtDNA transcription and replication. We suggest three mechanisms: (1) methylation within the non-coding D-loop, (2) methylation at gene start sites (GSS) and (3) post-translational modifications (PTMs) of TFAM. Unraveling mitochondrial gene expression regulation could open new therapeutic avenues for mitochondrial diseases.

Original languageEnglish
Pages (from-to)1099-1113
Number of pages15
JournalFrontiers in bioscience-Landmark
Volume22
DOIs
Publication statusPublished - 1-Mar-2017

Keywords

  • Mitochondrial epigenetics
  • MtDNA methylation
  • Gene expression
  • D-loop
  • TFAM
  • Review
  • HEAVY-STRAND PROMOTER
  • DNA METHYLATION
  • INSULIN-RESISTANCE
  • TRANSCRIPTION FACTOR
  • IN-VITRO
  • DIABETIC-RETINOPATHY
  • COLORECTAL-CANCER
  • DISPLACEMENT LOOP
  • CPG METHYLATION
  • DOWN-SYNDROME

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