Electron-transferring flavoprotein-ubiquinone oxidoreductase (ETF-QO) (ETF-QO)

Electron-transferring flavoprotein-ubiquinone oxidoreductase (ETF-QO), encoded by the ETFDH gene, is a 64-kDa flavoprotein located on the matrix side of the inner mitochondrial membrane [1, 2]. It plays a pivotal role in energy metabolism by linking the oxidation of fatty acids and several amino acids to the mitochondrial electron transport chain [1]. Specifically, ETF-QO accepts electrons from the electron-transferring flavoprotein (ETF) and transfers them to ubiquinone (Coenzyme Q10), thereby facilitating the production of ATP [1, 3]. Deficiencies in this enzyme result in Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), a clinically heterogeneous disorder that can manifest as severe neonatal metabolic crisis or late-onset lipid-storage myopathy [3, 4]. In many cases, particularly the late-onset form, the condition is highly responsive to pharmacological doses of riboflavin, which acts as a precursor to the FAD cofactor required for enzyme stability and activity [4]. Consequently, ETF-QO is a key target for nutritional and pharmacological interventions aimed at restoring metabolic flux in patients with fatty acid oxidation disorders [2, 4]. Beyond riboflavin, management often includes L-carnitine and Coenzyme Q10 to address secondary deficiencies and optimize mitochondrial function [4]. Sources: [1] UniProt (Q16134); [2] NCBI Gene (2110); [3] OMIM (231680); [4] PubMed (PMID: 25134611).

Other names

Electron-transferring-flavoprotein dehydrogenaseETFDHETF-ubiquinone oxidoreductaseETF dehydrogenase

Cofactor supplementation to stabilize enzyme structure and enhance catalytic activity