DNA polymerases in the mitochondria A critical review of the evidence

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.

The presence of rNTPs decreases the speed of mitochondrial DNA replication

“…Similarly, the primase/polymerase PrimPol can synthesize nucleic acids using both rNTPs and dNTPs, and has been shown to be involved in mtDNA maintenance [ 42 – 44 ]. Together, these and possibly other polymerases could influence the rNMP levels in mtDNA [ 45 ].…”

Mitochondrial DNA replication in mammalian cells: overview of the pathway

“…These polymerases are not essential for mtDNA maintenance and none of them can substitute for POLγ. Most likely they are involved in mtDNA repair, but the exact function of these additional polymerases in mtDNA maintenance needs to be further elucidated (reviewed in [ 12 ]).…”

“Mitochondrial Toolbox” – A Review of Online Resources to Explore Mitochondrial Genomics

“…MitoCarta 2.0 also includes a dataset containing images of 131 proteins for which mitochondrial localisation was assessed using mass spectrometry, green fluorescent protein tagging, and microscopy (Krasich and Copeland, 2017), and datasets indicating scores of mitochondrial localisation for over 20,000 human genes and 20,000 mouse genes, and datasets of human and mouse protein sequences (Calvo et al, 2016). MitoCarta 2.0 therefore serves as a reference database but does not include analytical tools accessible to users (Calvo et al, 2016).…”