Exploring a novel biological role of the master energy homeostasis regulator PGC1 a as a potential modifier of mitochondrial function and senescence

能量代谢的改变和线粒体功能障碍是衰老的已知特征，通过限制热量来控制线粒体功能可以延长生存时间。主要的能量调节因子PGC1 a通过参与线粒体生物发生和功能的基因的转录共激活，在控制抗氧化反应和能量代谢稳态中起关键作用。因此，它在肌肉、肝脏、脂肪细胞和神经元中起着关键的调节代谢功能。pgc1a依赖的调节通路在年龄和年龄相关疾病（肌肉萎缩、代谢和神经退行性疾病）中下调。除了具有良好的转录功能外，PGC1a还含有一个尚未被研究的假定的RNA识别基序。我们最近发现PGC1a直接结合RNA并驱动人类胚胎肾细胞中一些编码线粒体相关蛋白的PGC1a激活mrna的核输出（未发表的数据），可能将其新的核输出功能与其共同激活的转录本联系起来。

Alteration of the energy metabolism and mitochondrial dysfunction are known features of senescence and manipulating mitochondrial function through caloric restriction prolongs survival. The master energy regulator PGC1 a plays a pivotal role in controlling the antioxidant response and the energy metabolism homeostasis through transcriptional co-activation of genes involved in mitochondrial biogenesis and function. It therefore plays key egulatory metabolic functions in muscles, liver, adipocytes and neurons. PGC1a-dependent regulatory pathways are down-regulated in age and age-related diseases (muscle wasting, metabolic and neurodegenerative disorders). In addition to the well-characterised transcriptional function, PGC1a contains a putative RNA recognition motif which has not been investigated. We recently discovered that PGC1a directly binds RNA and drives the nuclear export of some PGC1a-activated mRNAs encoding mitochondrial-related proteins in human embryonic kidney cells (unpublished data) potentially linking its novel nuclear export function to the transcripts it co-activates.