Human mitochondrial DNA replication machinery and disease

Curr Opin Genet Dev. 2016 Jun;38:52-62. doi: 10.1016/j.gde.2016.03.005. Epub 2016 Apr 9.


The human mitochondrial genome is replicated by DNA polymerase γ in concert with key components of the mitochondrial DNA (mtDNA) replication machinery. Defects in mtDNA replication or nucleotide metabolism cause deletions, point mutations, or depletion of mtDNA. The resulting loss of cellular respiration ultimately induces mitochondrial genetic diseases, including mtDNA depletion syndromes (MDS) such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. Here we review the current literature regarding human mtDNA replication and heritable disorders caused by genetic changes of the POLG, POLG2, Twinkle, RNASEH1, DNA2, and MGME1 genes.

Publication types

  • Review

MeSH terms

  • Cell Respiration / genetics
  • DNA Helicases / genetics
  • DNA Polymerase gamma
  • DNA Replication / genetics*
  • DNA, Mitochondrial / genetics*
  • DNA-Directed DNA Polymerase / genetics
  • Exodeoxyribonucleases / genetics
  • Genome, Mitochondrial*
  • Humans
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Mitochondrial Proteins / genetics
  • Mutation
  • Ribonuclease H / genetics


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human
  • POLG2 protein, human
  • Exodeoxyribonucleases
  • MGME1 protein, human
  • Ribonuclease H
  • ribonuclease HI
  • DNA Helicases
  • DNA2 protein, human
  • TWNK protein, human