Mitochondrial alterations in a mouse model of Fragile X syndrome

Fragile X syndrome (FXS) is the most common form of hereditary mental retardation and results from the absence of Fragile X mental retardation protein, an RNA-binding protein that regulates the translation of several mRNAs. By a comparative proteomic analysis of cortical synaptosomes of 21 days old wild-type and Fmr1 knockout (KO) mice, a model of FXS, we found twenty-one differently expressed proteins, including up-regulated mitochondrial glycerol-3-phosphate dehydrogenase (mG3P-DH), a key component of the glycerophosphate shuttle. Furthermore, an increased activity of mG3P-DH and of all mitochondrial respiratory chain complexes was detected in Fmr1 KO mouse cortex at different ages, whereas no change occurred in the activity of cytoplasmic glycerol-3-phosphate dehydrogenase and key glycolytic enzymes. We show for the first time that in FXS the activities of mitochondrial enzymes are increased, suggesting a possible mitochondrial hyper-activation that could have potential implications in whole energy metabolism in this disorder.