果蝇 FMRP 的丢失导致能量代谢和线粒体功能的改变

Loss of Drosophila FMRP leads to alterations in energy metabolism and mitochondrial function.

模式动物：果蝇

组织：骨骼肌
作者：Weisz ED, Towheed A, Monyak RE, Toth MS, Wallace DC, Jongens TA 

出版期刊：《Hum Mol Genet》（2018）

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.

文章摘要：

脆性 X 综合征 (FXS) 是遗传性智力障碍的最普遍形式，也是自闭症最重要的单基因原因，是由 FMR1 基因的表达缺失引起的。在这里，我们表明dfmr1调节果蝇的全局代谢组。尽管我们之前发现脑胰岛素信号增加，但我们的结果表明dfmr1突变体减少了碳水化合物和脂质的储存，并且对饥饿压力过敏。观察到的代谢缺陷不能用摄食行为来解释，因为我们报告 dfmr1 突变体是过度吞噬的。相反，我们的数据将dfmr1确定为线粒体功能的调节剂。我们证明在过饱和条件下，dfmr1突变线粒体显着增加了最大电子传输系统（ETS）的能力。此外，间接飞行肌肉的电子显微照片揭示了dfmr1突变线粒体的惊人形态变化。总之，我们的结果说明了dfmr1对于适当维持营养稳态和线粒体功能的重要性。

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