2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial

DECR1 (2,4-dienoyl-CoA reductase) is a mitochondrial enzyme that catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to trans-3-enoyl-CoA, functioning as an auxiliary enzyme in beta-oxidation of unsaturated fatty acids (UniProt: Q16698). The protein participates in the metabolism of polyunsaturated fatty acyl-CoA esters within mitochondria, supporting cellular energy metabolism. Mutations in DECR1 cause 2,4-dienoyl-CoA reductase deficiency (DECRD; MIM 616034), a rare autosomal recessive disorder characterized by severe early-onset encephalopathy with neurologic dysfunction and metabolic abnormalities including elevated lysine and C10:2 carnitine levels.

In Alzheimer's Disease, DECR1 is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of +0.26 across analyzed subcellular fractions from TMT-labeled tandem mass spectrometry. This modest elevation suggests altered fatty acid metabolism and mitochondrial function may be relevant to AD pathophysiology, consistent with emerging evidence linking metabolic dysfunction to neurodegeneration.