Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy.
Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy.
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DOI：
10.1371/journal.pone.0168182
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Simonsen A
中科院分区：
文献类型：
--
作者：
Aas A;Isakson P;Bindesbøll C;Alemu EA;Klungland A;Simonsen A
FTO（脂肪量和肥胖）基因的多态性变体与人类的体重指数相关，但其潜在的分子机制尚未确定。FTO通过氨基酸传感与能量稳态相关，并被认为激活雷帕霉素复合物1的哺乳动物靶标，雷帕霉素复合物1是自噬的负调节剂。FTO定位于细胞核和细胞质，在这项研究中，我们确定了一个功能性的核定位信号（NLS）在N-末端的FTO，以及核定位信息在其C-末端。FTO核转运的抑制对自噬没有影响，并且与先前提出的FTO在自噬中的作用相反，我们发现与耗尽FTO的一组细胞类型相比，对照细胞中饥饿诱导的自噬没有差异。未来进一步研究FTO的细胞功能对于理解FTO变异与体重相关的原因将是重要的。
Polymorphic variants of the FTO (fat mass and obesity) gene associate with body mass index in humans, but the underlying molecular mechanisms have not been firmly determined. FTO is linked to energy homeostasis via amino acid sensing and is thought to activate the mammalian target of rapamycin complex 1, a negative regulator of autophagy. FTO localises both to the nucleus and the cytoplasm, and in this study we identify a functional nuclear localisation signal (NLS) in the N-terminus of FTO, as well as nuclear localization information in its very C-terminus. Inhibition of FTO nuclear transport has no effect on autophagy and in contrast to a previously proposed role of FTO in autophagy, we find no difference in starvation-induced autophagy in control cells compared to a panel of cell types depleted of FTO. Future studies that further characterise the cellular functions of FTO will be important to understand why variants in FTO are associated with body weight.