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

探索主能量稳态调节因子 PGC1a 作为线粒体功能和衰老的潜在调节剂的新生物学作用

• 批准号: 2594369
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2594369
• 关键词: Exploring; novel; biological; role; master

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nuclear export of some PGC1a-activated mRNAs encoding mitochondrial-related proteins in human embryonic kidney cells (unpublished data) potentially linking its novel nuclear export function to the transcripts it co-activates.

能量代谢的改变和线粒体功能障碍是衰老的已知特征，并且通过热量限制来操纵线粒体功能以维持生存。主能量调节因子PGC1a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发挥关键的分泌代谢功能。PGC1a依赖性调节途径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。除了充分表征的转录功能，PGC1a含有一个假定的RNA识别基序，尚未进行研究。我们最近发现，PGC1a直接结合RNA，并驱动一些PGC1a激活的mRNA的核输出，这些mRNA编码人胚肾细胞中的肾脏相关蛋白（未发表的数据），可能将其新的核输出功能与其共激活的转录本联系起来。