Abstract 2779 Quantification of 2-Hydroxyglutarate Enantiomers in the Ndufs4 Knockout Mouse

The Ndufs4-/- mouse is a model of the mitochondrial disease Leigh syndrome (LS). Mutations in the human homolog NDUFS4 cause LS with reduced ATP synthesis by oxidative phosphorylation. The Ndufs4-/- mouse exhibits brainstem and olfactory bulb degeneration and typically dies due to respiratory failure attributed to brainstem pathology. We recently showed that these mice have decreased activity of the a-ketoglutarate (AKG) dehydrogenase complex-, with subsequent reduced succinyl CoA production and substrate level phosphorylation.