protein
3-ketoacyl-CoA thiolase, mitochondrial
Gene
ACAA2
Organism
Homo sapiens(9606)
Length
397 aa
Mass
41,924 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+0.465
S3
+0.294
Mean log₂FC across detected fractions: +0.3793 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
In the production of energy from fats, this is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (Probable). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain unbranched 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (Probable). Also catalyzes the condensation of two acetyl-CoA molecules into acetoacetyl-CoA and could be involved in the production of ketone bodies (Probable). Also displays hydrolase activity on various fatty acyl-CoAs (PubMed:25478839). Thereby, could be responsible for the production of acetate in a side reaction to beta-oxidation (Probable). Abolishes BNIP3-mediated apoptosis and mitochondrial damage (PubMed:18371312)
Sources
Last updated 5/8/2026, 6:38:46 AM