Mutation in DNA polymerase γ: mitochondrial disorders

Abstract

Together with key components of the mitochondrial DNA (mtDNA) replication machinery, DNA polymerase γ (POLG) replicates the human mitochondrial genome. Defects in mtDNA replication or nucleotide metabolism result in mtDNA deletions, point mutations, or depletion. The resulting loss of cellular respiration ultimately causes mitochondrial genetic diseases, such as mtDNA deletion disorders, progressive external ophthalmoplegia, ataxia- neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy, as well as mtDNA depletion syndromes like Alpers or early infantile hepatocerebral syndromes. This review paper provides an overview of the most recent research on the role of POLG in the manifestation of mitochondrial diseases.