Acyl-CoA synthetase family member 3 (ACSF3)

Acyl-CoA synthetase family member 3 (ACSF3) is a mitochondrial enzyme responsible for activating malonate and methylmalonate by converting these dicarboxylic acids to their respective CoA thioesters (malonyl-CoA and methylmalonyl-CoA) through an ATP-dependent reaction mechanism similar to other acyl-CoA synthetases. This process is fundamental for mitochondrial fatty acid synthesis (mtFAS) and for preventing cellular toxicity due to accumulated malonate, which is a potent inhibitor of mitochondrial respiration. Pathogenic mutations in ACSF3 cause combined malonic and methylmalonic aciduria (CMAMMA), an inherited metabolic disorder characterized by developmental, neurological, and metabolic symptoms resulting from the accumulation of organic acids. Emerging evidence suggests roles in other diseases such as hepatic steatosis and COPD, mainly through genetic or epigenetic regulation. ACSF3 is considered an important therapeutic and diagnostic target primarily in the context of inherited metabolic disease.

Other names

Malonate--CoA ligase ACSF3, mitochondrialMalonyl-CoA synthetaseAcyl-CoA synthetase family member 3, mitochondrialACSF3_HUMANPSEC0197

For potential modulators: Activation or stabilization of SIRT3 leads to ACSF3 deacetylation and proteolysis, reducing malonyl-CoA synthetase activity and affecting lipid and energy metabolism. (No direct inhibitors or activators currently identified)