The yeast NDI1 protein is sufficient to rescue lifespan in a mouse model of Leigh Syndrome due to loss of mitochondrial complex I subunit NDUFS4. (A) Schematic of the mitochondrial electron transport chain with ectopic NDI1. (B) Basal oxygen consumption rate (OCR) of cerebellar granular neurons (CGNs) from postnatal day 2–7 mice. Data pooled from 6 independent experiments (N=7–14, ANOVA P=0.0008, Dunnett’s test to WT *P<0.05). (C) ATP-coupled OCR in CGNs with the ATPase inhibitor Oligomycin A. Data pooled from 4 independent experiments (N=4–11, ANOVA P=0.0008, Dunnett’s test to WT *P<0.05). (D) Percentage of basal OCR that is resistant to MC1 inhibitor Piericidin A at 500nM. (N=3–5, ANOVA P<0.0001, * P<0.05 Dunnett’s test to WT). (E) Kaplan-Meier curves of cKO vs cKO + NDI1. (N=40–59, Log-rank test P<0.0001). (F) Body weight in grams, cKO + NDI1 indicates 2 alleles of NDI1. (N=21–38, ANOVA P<0.0001, Dunnett’s test to Cre control P<0.0001). Data represent mean ± SEM.