Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex (DLST) (DLST)

The Oxoglutarate dehydrogenase complex (OGDC), specifically the E2 lipoyl domain of the dihydrolipoyllysine-residue succinyltransferase (DLST) subunit, is a critical component of the mitochondrial tricarboxylic acid (TCA) cycle (UniProt P36957). It catalyzes the conversion of alpha-ketoglutarate to succinyl-CoA, a key step in cellular energy production and biosynthetic precursor generation (NCBI Gene ID: 1743). The E2 subunit contains a lipoyl domain where a lipoic acid cofactor is covalently attached to a lysine residue, facilitating the transfer of the succinyl group. In pathology, DLST is a primary autoantigen in Primary Biliary Cholangitis (PBC) (PMID: 10448858) and has been implicated in neurodegenerative disorders like Alzheimer's disease due to reduced enzymatic activity (PMID: 9129721). Furthermore, DLST is a therapeutic target in oncology; the drug devimistat (CPI-613) inhibits this complex to starve cancer cells of energy and metabolic intermediates (PMID: 23161301). Targeting this domain requires careful consideration of systemic metabolic impacts, as it is essential for normal mitochondrial function across most tissues.

Other names

Dihydrolipoyl succinyltransferaseE2 component of OGDC2-oxoglutarate dehydrogenase complex component E2DLTSOxoglutarate dehydrogenase complex, E2 lipoyl domain

Devimistat (CPI-613) inhibits the E2 subunit (DLST) of the oxoglutarate dehydrogenase complex and the pyruvate dehydrogenase complex, disrupting the TCA cycle and inducing apoptosis in cancer cells (PMID: 23161301).