Metformin treatment normalizes decreased oxidative phosphorylation protein content in RTT mouse hippocampus. Protein expression levels of SDHB (subunit of Complex II) (c) and UQCRC2 (subunit of Complex III) (d) is decreased in the hippocampus of RTT mice. A trend towards a decrease was also observed for ATP5A (subunit of Complex V) (f) in RTT compared to WT controls. No genotype differences were found for NDUFB8 (subunit of Complex I) (b) and MTCO1 (subunit of Complex IV) (e). Metformin treatment normalized protein expression levels of SDHB (subunit of Complex II) (c) and ATP5A (subunit of Complex V) (f) in RTT mice. Representative blot is shown in (a). N = 9–11. Data are mean ± SEM normalized for WT, sal. Statistical significance was calculated by two-way ANOVA, with Tukey’s post hoc test. * p < 0.05, ** p < 0.01. WT: wild-type mice; RTT: MeCP2-308 heterozygous female mice; sal: saline; met: metformin; NDUFB8: NADH:Ubiquinone Oxidoreductase Subunit B8; SDHB: Succinate Dehydrogenase Complex Iron Sulfur Subunit B; UQCRC2: Ubiquinol-Cytochrome C Reductase Core Protein II; MTCO1: mitochondrially encoded cytochrome c oxidase I; ATP5A: ATP Synthase, H+ Transporting, Mitochondrial F1 Complex.