Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO)

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a nuclear-encoded mitochondrial enzyme essential for the oxidation of fatty acids and certain amino acids. Located in the inner mitochondrial membrane, it accepts electrons from electron-transferring flavoprotein (ETF) and transfers them to the ubiquinone pool in the respiratory chain, thereby linking primary metabolism to ATP production (UniProt, Q16134). Dysfunction of this enzyme, typically due to mutations in the ETFDH gene, results in Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), a metabolic disorder characterized by the inability to break down fats and proteins for energy (NCBI Gene, 2110). Clinically, this leads to symptoms ranging from neonatal-onset metabolic acidosis to late-onset lipid-storage myopathy (OMIM, 231680). While not a target for inhibition, ETF-QO is a primary target for therapeutic intervention via riboflavin supplementation, which stabilizes the enzyme and enhances its residual activity in many patients (PubMed, PMID: 30114118). Additionally, it is a candidate for emerging gene therapy approaches aimed at restoring functional enzyme levels in severe cases. The enzyme's role as a metabolic hub makes it a critical focus for managing systemic energy deficits and preventing toxic metabolite accumulation. Monitoring of acylcarnitine profiles and organic acids is standard for assessing the efficacy of treatments targeting this pathway.

Other names

Electron-transferring-flavoprotein dehydrogenaseETFDHETF dehydrogenaseETF-ubiquinone oxidoreductase

Cofactor supplementation to stabilize enzyme structure and enhance residual catalytic activity.