Electron transfer flavoprotein subunit alpha, mitochondrial

Electron transfer flavoprotein subunit alpha (ETFA, also Alpha-ETF) is a mitochondrial heterodimeric protein that accepts electrons from multiple acyl-CoA dehydrogenases and other metabolic enzymes, transferring them to the respiratory chain via ETF-ubiquinone oxidoreductase (UniProt: P13804). This electron transport function is essential for normal mitochondrial fatty acid oxidation and amino acid metabolism. Mutations in ETFA cause glutaric aciduria 2A, an autosomal recessive metabolic disorder characterized by multiple acyl-CoA dehydrogenase deficiencies and accumulation of organic acids (UniProt: P13804).

In Alzheimer's Disease, ETFA is significantly downregulated in post-mortem human brain tissue (mean log2 fold-change −0.39) compared to age-matched controls, as measured by quantitative proteomics (Chaparral AD proteomics). This reduction suggests impaired mitochondrial energy metabolism and fatty acid oxidation capacity in AD brain, consistent with emerging evidence of mitochondrial dysfunction in neurodegeneration. The directional downregulation across brain fractions indicates a consistent loss of this metabolic enzyme in the disease state.