Table 1 Common mutations in genes or gene groups resulting in mitochondrial-associated metabolic diseases
From: Mitochondrial-associated metabolic disorders: foundations, pathologies and recent progress
Gene(s) | Location | Product | Function | Phenotype | Associated diseases |
|---|---|---|---|---|---|
COQ2, COQ9, PDSS1/2, ADCK3 | Nuclear | Coenzyme Q10 (CoQ) | Required for synthesis of CoQ; CoQ is an essential electron shuttle, acts as antioxidant, cofactor of pyrimidine synthesis | Decreased ETC activity; Skeletal muscle breakdown | CoQ deficiency |
ETC subunits | Mitochondrial | Mitochondrial respiratory complex subunits | Oxidative phosphorylation | Respiratory complex deficiency | Mitochondrial myopathy; Lactic acidosis; MELAS (complex I) |
ETFDH | Nuclear | Electron-transferring-flavoprotein dehydrogenase | Required for delivering electrons to complex III; derived from fatty acid and amino acid oxidation | Accumulation of toxic intermediates from fatty acid and amino acid oxidation; Decreased ETC efficiency | Symptoms of glutaric acidemia type 2 |
POLG, POLG2 | Nuclear | Mitochondrial DNA polymerase gamma | mtDNA replication | mtDNA depletion | mtDNA depletion syndrome; Symptoms of MNGIE |
12S rRNA, 16S rRNA | Mitochondrial | Mitochondrial ribosomal RNAs | Required for synthesis of mtDNA-encoded proteins | Respiratory complex deficiency | Mitochondrial myopathy; Lactic acidosis |
tRNAs | Mitochondrial | Mitochondrial transfer RNAs | Required for synthesis of mtDNA-encoded proteins | Respiratory complex deficiency | Mitochondrial myopathy; Lactic acidosis; MELAS |
TYMP | Nuclear | Thymidine phosphorylase | Required for processing thymidine and deoxyuridine into thymine and uracil | Accumulation of thymidine and deoxyuridine; Imbalance in mitochondrial (d)NTP pool; Impaired mtDNA replication and transcription | MNGIE |