Weisz 2018 Hum Mol Genet

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Weisz ED, Towheed A, Monyak RE, Toth MS, Wallace DC, Jongens TA (2018) Loss of Drosophila FMRP leads to alterations in energy metabolism and mitochondrial function. Hum Mol Genet 27:95-106.

» PMID: 29106525

Weisz ED, Towheed A, Monyak RE, Toth MS, Wallace DC, Jongens TA (2018) Hum Mol Genet

Abstract: Fragile X Syndrome (FXS), the most prevalent form of inherited intellectual disability and the foremost monogenetic cause of autism, is caused by loss of expression of the FMR1 gene. Here, we show that dfmr1 modulates the global metabolome in Drosophila. Despite our previous discovery of increased brain insulin signaling, our results indicate that dfmr1 mutants have reduced carbohydrate and lipid stores and are hypersensitive to starvation stress. The observed metabolic deficits cannot be explained by feeding behavior, as we report that dfmr1 mutants are hyperphagic. Rather, our data identify dfmr1 as a regulator of mitochondrial function. We demonstrate that under supersaturating conditions, dfmr1 mutant mitochondria have significantly increased maximum electron transport system (ETS) capacity. Moreover, electron micrographs of indirect flight muscle reveal striking morphological changes in the dfmr1 mutant mitochondria. Taken together, our results illustrate the importance of dfmr1 for proper maintenance of nutrient homeostasis and mitochondrial function.

Bioblast editor: Kandolf G O2k-Network Lab: US PA Philadelphia Wallace DC

Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Autism, Neurodegenerative 

Organism: Drosophila  Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k