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

The Oxoglutarate dehydrogenase complex E2 subunit, scientifically known as Dihydrolipoyllysine-residue succinyltransferase (DLST), is a core enzymatic component of the multi-enzyme alpha-ketoglutarate dehydrogenase complex (KGDHC) located within the mitochondrial matrix (UniProt P36957). It plays a pivotal role in the tricarboxylic acid (TCA) cycle by catalyzing the transfer of a succinyl group to coenzyme A, a step essential for aerobic energy production and cellular respiration (NCBI Gene ID: 1743). DLST is clinically significant as a major autoantigen in primary biliary cholangitis, where patients typically present with anti-mitochondrial antibodies (AMA) targeting this subunit (Fussey et al., 1988, PubMed: 3263550). In neurobiology, reduced activity of the DLST-containing complex is a consistent metabolic hallmark of Alzheimer's disease and other neurodegenerative conditions (Gibson et al., 2000, PubMed: 10952014). Furthermore, DLST is a therapeutic target in oncology; the small molecule inhibitor devimistat (CPI-613) targets the E2 subunits of both KGDHC and the pyruvate dehydrogenase complex to exploit the metabolic dependencies of cancer cells (Zachar et al., 2011, PubMed: 21610110). Targeting this enzyme aims to disrupt the metabolic flexibility of tumors, although the central importance of the TCA cycle in normal physiology presents challenges for systemic safety.

Other names

Oxoglutarate dehydrogenase complex E2 subunitDihydrolipoyl transsuccinylaseDLTSE2 component of the alpha-ketoglutarate dehydrogenase complexDihydrolipoyllysine-residue succinyltransferase

Inhibition of the alpha-ketoglutarate dehydrogenase complex and pyruvate dehydrogenase complex, leading to the disruption of mitochondrial metabolism and induction of apoptosis in cancer cells (Zachar et al., 2011, PubMed: 21610110).