Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial

DLAT (dihydrolipoyllysine-residue acetyltransferase) is the E2 component of the pyruvate dehydrogenase (PDH) complex, a key mitochondrial enzyme that catalyzes acetyl-CoA production from pyruvate, thereby linking glycolysis to the tricarboxylic acid cycle (UniProt: P10515). The protein accepts and transfers acetyl groups from acetyl-lipoyl moieties generated by the PDH E1 component to coenzyme A, facilitating central energy metabolism.

DLAT is expressed in mitochondria across tissues. Mutations in DLAT cause pyruvate dehydrogenase E2 deficiency, a rare metabolic disorder characterized by lactic acidosis and neurological dysfunction, including dystonia, hypotonia, and ataxia in infancy and early childhood (UniProt: P10515). The severe neurological features underscore the critical role of PDH in neural energy homeostasis.

In Alzheimer's disease, DLAT shows ambiguous regulation across subcellular fractions in post-mortem AD brain relative to age-matched controls (mean log2FC −0.0107 across 4 fractions; Chaparral AD proteomics). This modest, direction-inconsistent change suggests mild or fraction-dependent alterations in PDH E2 abundance in AD, warranting further investigation into whether impaired pyruvate metabolism contributes to AD pathogenesis.