2-oxoglutarate dehydrogenase-like, mitochondrial

OGDHL (2-oxoglutarate dehydrogenase-like, mitochondrial) is a mitochondrial enzyme that functions as an E1-like component of the 2-oxoglutarate dehydrogenase multienzyme complex (OGDHC). It catalyzes the decarboxylation of alpha-ketoglutarate in the tricarboxylic acid cycle, converting 2-oxoglutarate to succinyl-CoA and CO2 while reducing NAD+ to NADH (UniProt: Q9ULD0). The protein is also involved in inhibiting cell proliferation and promoting apoptosis.

OGDHL localizes to mitochondria where it participates in central metabolic energy production. Beyond its metabolic role, biallelic variants in OGDHL cause Yoon-Bellen neurodevelopmental syndrome (YOBELN, MIM 619701), an autosomal recessive disorder featuring global developmental delay and intellectual disability, sometimes accompanied by hypotonia, ataxia, seizures, and brain imaging abnormalities (UniProt: Q9ULD0).

In Alzheimer's disease brain tissue, OGDHL is significantly downregulated relative to age-matched controls (mean log2 fold-change: −0.72; Chaparral AD proteomics). This reduction was observed across 2 of 4 subcellular fractions in human post-mortem AD brain analyzed by quantitative proteomics, suggesting compromised mitochondrial energy metabolism in the disease state.