The mitochondrial DNA polymerase in health and disease

Abstract

Since mutations in mitochondrial DNA (mtDNA) have been shown to be a cause of many mitochondrial diseases as well as aging, it is important to understand the origin of these mutations and how replication proteins modulate this process. DNA polymerase γ (pol γ) is the polymerase that is responsible for replication and repair of mtDNA. Pol γ has three main roles in mtDNA maintenance and mutagenesis. As the only known DNA polymerase in mitochondria, pol γ is required for all replication and repair functions and is the main source of errors produced in human mtDNA. Pol γ is also sensitive to a host of antiviral nucleoside analogs used to treat HIV-1 infections, which can cause an induced mitochondrial toxic-ity. Finally, the gene for pol γ, POLG, is a genetic locus for several mitochondrial disease with over 150 genetic mutations currently identified.