Deoxyguanosine kinase, mitochondrial (DGUOK)

Deoxyguanosine kinase, mitochondrial (DGUOK) is a nuclear-encoded enzyme that resides in the mitochondrial matrix, where it serves as the rate-limiting catalyst for the phosphorylation of purine deoxyribonucleosides into their monophosphate forms. This activity is essential for the mitochondrial deoxynucleoside salvage pathway, which maintains the balanced pool of deoxyribonucleoside triphosphates (dNTPs) required for mitochondrial DNA (mtDNA) replication and repair, particularly in non-dividing cells. Mutations in the DGUOK gene are a primary cause of hepatocerebral mitochondrial DNA depletion syndrome, a severe condition characterized by early-onset liver failure and neurological deterioration. Beyond its role in genetic disorders, DGUOK is a critical therapeutic target due to its ability to activate various purine nucleoside analog prodrugs used in antiviral and antineoplastic therapies, such as ganciclovir and cladribine. Recent research also highlights its involvement in cancer progression, specifically in lung adenocarcinoma, where its overexpression promotes mitochondrial oxidative phosphorylation and cancer stem cell self-renewal. Consequently, DGUOK is being explored both as a target for gene therapy to restore function in deficiency syndromes and as a potential target for small-molecule inhibitors to impair mitochondrial metabolism in malignant cells.

Other names

dGKDGKDeoxyadenosine kinase, mitochondrialMTDPS3NCPHPEOB4NCPH1

Phosphorylates purine deoxyribonucleosides (deoxyguanosine and deoxyadenosine) into their respective monophosphates (dGMP and dAMP) within the mitochondrial matrix, serving as the rate-limiting step in the mitochondrial purine salvage pathway.