Abhydrolase domain-containing protein 11 (ABHD11)

Abhydrolase domain-containing protein 11 (ABHD11) is a mitochondrial enzyme in the alpha/beta hydrolase family. It plays a critical role in regulating mitochondrial lipid and 2-oxoglutarate (2-OG) metabolism by maintaining the functional lipoylation of the 2-oxoglutarate dehydrogenase complex (OGDHc), thus supporting TCA cycle activity and modulating 2-OG-dependent dioxygenase function. Loss or inhibition of ABHD11 disrupts these processes, leading to accumulation of 2-OG and stabilization of HIF-1α, thereby affecting oxygen-sensing pathways, histone modifications, and DNA methylation. ABHD11 is also involved in the regulation of intracellular lipid stores and may be relevant in obesity and cancer biology. Genetic deletions of ABHD11 are linked to Williams-Beuren syndrome. Selective inhibitors such as ML226 allow pharmacological targeting of ABHD11 for research and potential therapeutic intervention.

Other names

Alpha/beta hydrolase domain-containing protein 11ABHDB

Inhibition of ABHD11 impairs OGDHc lipoylation, leading to accumulation of 2-OG and deregulation of 2-OG-dependent dioxygenases\n- Inhibition of ABHD11 leads to HIF-1α stabilization due to impaired prolyl hydroxylation as a result of increased 2-OG