A diagram showing the proteins that are involved in mtDNA maintenance and known to be associated with mtDNA maintenance defects
Enzymes of the mitochondrial nucleotide salvage pathway. Thymidine kinase 2 (TK2; encoded by TK2) and deoxyguanosine kinase (DGK; encoded by DGUOK) convert the deoxyribonucleosides to deoxyribonucleotide monophosphates. Nucleotide monophosphate kinase (NMPK) converts deoxyribonucleotide monophosphates to deoxyribonucleotide diphosphates. Nucleotide diphosphate kinase (NDPK) converts deoxyribonucleotide diphosphates to deoxyribonucleotide triphosphates. NDPK forms a complex with both succinyl-CoA ligase (SUCL) (composed of an alpha subunit encoded by SUCLG1 and a beta subunit encoded by either SUCLA2 or SUCLG2) and gamma-aminobutyrate transaminase (GABAT), encoded by ABAT.
Enzymes of cytosolic nucleotide metabolism. Ribonucleotide reductase (RNR) composed of two catalytic subunits and two small subunits (either R2 or p53-inducible small RNR subunit [p53R2; encoded by RRM2B]) converts ribonucleotide diphosphates to deoxyribonucleotide diphosphates. Thymidine phosphorylase (TP; encoded by TYMP) converts thymidine to thymine.
Proteins involved in mitochondrial nucleotide transport. Adenine nucleotide translocator 1 (ANT1; encoded by SLC25A4), acylglycerol kinase (AGK; encoded by AGK), and MPV17 (encoded by MPV17)
Enzymes involved in mtDNA replication. Twinkle (encoded by TWNK), a DNA helicase that separates the DNA strands (DNA polymerase γ [pol γ], consisting of a catalytic subunit encoded by POLG, and two accessory subunits encoded by POLG2) requires an RNA primer to initiate DNA replication. Mitochondrial transcription factor A (TFAM; encoded by TFAM), is required for the generation of an RNA primer. Nucleases removing RNA primers and flap intermediates are RNase H1 (encoded by RNASEH1), DNA helicase/nuclease 2 (DNA2; encoded by DNA2), and mitochondrial genome maintenance exonuclease 1 (MGME1; encoded by MGME1).
Proteins involved in mitochondrial fusion. Mitofusin 2 (MFN2; encoded by MFN2), dynamin-related GTPase OPA1 (encoded by OPA1), and F-box and leucine-rich repeat 4 (FBXL4; encoded by FBXL4)
