DNA polymerase subunit gamma (POLG) (POLG)

DNA polymerase subunit gamma (POLG) is the primary enzyme responsible for the replication and repair of mitochondrial DNA (mtDNA) in human cells [UniProt: P54098]. It functions as a heterotrimer consisting of a catalytic subunit (encoded by the POLG gene) and a dimeric accessory subunit (encoded by POLG2) that enhances DNA binding and processivity [PubMed: 29102396]. POLG is essential for maintaining the integrity and copy number of the mitochondrial genome, which is vital for oxidative phosphorylation and cellular energy production [PubMed: 18544031]. Mutations in the POLG gene are a leading cause of inherited mitochondrial diseases, manifesting as a wide spectrum of clinical phenotypes including Alpers-Huttenlocher syndrome and progressive external ophthalmoplegia [NIH: GeneReviews]. Furthermore, POLG is a significant site of off-target toxicity for several nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV treatment, which can inhibit the enzyme and lead to mitochondrial depletion and systemic side effects like lactic acidosis [PubMed: 11518513]. Additionally, certain medications like valproic acid are strictly contraindicated in patients with POLG mutations due to the risk of acute liver failure [PubMed: 23430455]. Understanding POLG function is critical for both diagnosing genetic mitochondrial disorders and managing drug-induced mitochondrial toxicities.

Other names

POLG1PCLGMDP1Mitochondrial DNA polymerase catalytic subunitMIRASSANDOSCAE

Inhibition of mitochondrial DNA polymerase activity by nucleoside reverse transcriptase inhibitors (NRTIs), leading to mitochondrial DNA depletion and dysfunction [PubMed: 11518513].