Oxoglutarate dehydrogenase-like (OGDHL)

Oxoglutarate dehydrogenase-like (OGDHL) is a mitochondrial enzyme that functions as the E1 component of the 2-oxoglutarate dehydrogenase complex (OGDHC). It plays a critical role in the tricarboxylic acid (TCA) cycle by catalyzing the oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA (UniProt Q9ULD0). While its homolog OGDH is ubiquitously expressed, OGDHL shows more restricted expression, particularly in the brain and liver, and is often downregulated in various malignancies such as colorectal and gastric cancers (PMID: 28656234). This downregulation is frequently linked to promoter hypermethylation, suggesting that OGDHL acts as a metabolic tumor suppressor by regulating flux through the TCA cycle and modulating reactive oxygen species (ROS) production (PMID: 30106634). Therapeutic interest in OGDHL stems from its role in cancer metabolism, where drugs like devimistat (CPI-613) target the OGDHC to induce apoptosis in tumor cells by exploiting their altered metabolic states (NCI Drug Dictionary). Understanding OGDHL's specific regulatory mechanisms offers potential for developing targeted metabolic therapies and diagnostic biomarkers in oncology.

Other names

2-oxoglutarate dehydrogenase-like, mitochondrialOGDH-like2-oxoglutarate dehydrogenase complex component E1-likeOGDHL

Inhibition of the mitochondrial alpha-ketoglutarate dehydrogenase complex, disrupting the TCA cycle and inducing mitochondrial stress.