Acetyl-CoA acetyltransferase, mitochondrial

ACAT1 (Acetyl-CoA acetyltransferase, mitochondrial) is a mitochondrial enzyme that catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and shorter fatty acyl-CoA species (UniProt: P24752). This reversible activity represents the final step of mitochondrial beta-oxidation. The enzyme also catalyzes condensation of two acetyl-CoA molecules into acetoacetyl-CoA and thereby plays a major role in ketone body metabolism (UniProt: P24752).

ACAT1 is primarily involved in fatty acid catabolism and ketone body synthesis in mitochondria. A genetic disorder of ACAT1 function—3-ketothiolase deficiency (3KTD)—is an autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks (UniProt: P24752).

ACAT1 is associated with Alzheimer's Disease pathology. In human post-mortem AD brain tissue compared to age-matched controls, ACAT1 expression is upregulated with a mean log₂ fold-change of 0.13 across 2 subcellular fractions analyzed by TMT-labeled quantitative proteomics (Chaparral AD proteomics). This modest elevation may reflect altered mitochondrial metabolism or energy substrate utilization in AD pathology.