DNA polymerases in the mitochondria: A critical review of the evidence

Front Biosci (Landmark Ed). 2017 Jan 1;22:692-709. doi: 10.2741/4510.

Abstract

Since 1970, the DNA polymerase gamma (PolG) has been known to be the DNA polymerase responsible for replication and repair of mitochondrial DNA, and until recently it was generally accepted that this was the only polymerase present in mitochondria. However, recent data has challenged that opinion, as several polymerases are now proposed to have activity in mitochondria. To date, their exact role of these other DNA polymerases is unclear and the amount of evidence supporting their role in mitochondria varies greatly. Further complicating matters, no universally accepted standards have been set for definitive proof of the mitochondrial localization of a protein. To gain an appreciation of these newly proposed DNA polymerases in the mitochondria, we review the evidence and standards needed to establish the role of a polymerase in the mitochondria. Employing PolG as an example, we established a list of criteria necessary to verify the existence and function of new mitochondrial proteins. We then apply this criteria towards several other putative mitochondrial polymerases. While there is still a lot left to be done in this exciting new direction, it is clear that PolG is not acting alone in mitochondria, opening new doors for potential replication and repair mechanisms.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • DNA Polymerase beta / genetics
  • DNA Polymerase beta / metabolism
  • DNA Polymerase gamma / genetics
  • DNA Polymerase gamma / metabolism
  • DNA Primase / genetics
  • DNA Primase / metabolism
  • DNA, Mitochondrial / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Humans
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Multifunctional Enzymes / genetics
  • Multifunctional Enzymes / metabolism
  • Mutation

Substances

  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Multifunctional Enzymes
  • DNA Polymerase beta
  • DNA Primase
  • DNA polymerase theta
  • DNA polymerase zeta
  • PrimPol protein, human
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human
  • REV3L protein, human
  • Rad30 protein