3-ketoacyl-CoA thiolase, mitochondrial

ACAA2 (3-ketoacyl-CoA thiolase, mitochondrial) is a 41.9 kDa enzyme that catalyzes the final step of mitochondrial beta-oxidation, cleaving medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and shorter fatty acyl-CoA molecules (UniProt: P42765). The protein also participates in ketone body production and displays hydrolase activity on various fatty acyl-CoAs. Additionally, ACAA2 can suppress BNIP3-mediated apoptosis and mitochondrial damage, suggesting a role in cellular survival mechanisms (UniProt: P42765).

ACAA2 functions in cellular energy metabolism via mitochondrial fatty acid oxidation, a central pathway for ATP generation from lipids. No Alzheimer's Disease or autism spectrum disorder associations are annotated in the UniProt disease field (UniProt: P42765).

In Alzheimer's Disease, ACAA2 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log₂ fold-change of +0.38 across two subcellular fractions in TMT-labeled mass spectrometry analysis (Chaparral AD proteomics). This upregulation suggests increased mitochondrial fatty acid catabolism or potential compensatory metabolic remodeling in AD pathology, though the biological significance requires further investigation.