Acyl-coenzyme A thioesterase 2, mitochondrial (ACOT2)

Acyl-coenzyme A thioesterase 2, mitochondrial (ACOT2), is a mitochondrial matrix enzyme belonging to the acyl-CoA thioesterase (ACOT) family and the type I α/β hydrolase fold class. ACOT2 catalyzes the hydrolysis of acyl-CoA thioesters—especially medium- and long-chain fatty acyl-CoA esters—producing free fatty acids and coenzyme A (CoA), thus regulating levels of these metabolites within the cell. This activity is essential for proper mitochondrial fatty acid β-oxidation, by maintaining the availability of free CoA and preventing toxic accumulation of acyl-CoA intermediates, particularly in energy-dependent tissues such as liver, heart, skeletal muscle, and brown adipose tissue. ACOT2 can influence cellular adaptation to metabolic stress, as evidenced by gene expression changes in metabolic disorders (including type 2 diabetes mellitus and non-alcoholic fatty liver disease), and it has also been linked to viral pathophysiology, as its knockdown suppresses dengue virus replication—highlighting a role in viral life cycle regulation via lipid remodeling. The protein is monomeric, resides in the mitochondrial matrix, and its structure features an N-terminal β-sandwich and a C-terminal α/β hydrolase catalytic domain that contains a Ser-His-Asp catalytic triad for enzymatic activity.

Other names

ZAP128MTE1CTE-IAPTE2ACTE1AACOT2PTE2acyl-coenzyme A thioesterase 2, mitochondrialacyl-coenzyme A thioester hydrolase 2along-chain acyl-CoA thioesterase 2mitochondrial acyl-CoA thioesterase 1peroxisomal long-chain acyl-coA thioesterase 2

Hydrolysis of acyl-CoA to free fatty acid and coenzyme A; modulates substrate availability for mitochondrial β-oxidation