Leigh syndrome is a fatal pediatric neurodegenerative disorder caused by mitochondrial dysfunction, most often due to defects in the mitochondrial respiratory chain. The Ndufs4 knockout (Ndufs4 KO) mouse is an established model of the disease, as loss of the NDUFS4 subunit leads to complex I (CI) deficiency and reproduces the neurological decline and pathology seen in affected children. Researchers from The Children’s Hospital of Philadelphia Research Institute and collaborators described how NV-354, a water-soluble prodrug of succinate, may mitigate this mitochondrial dysfunction.