Mitochondrial genes and TOR signaling in Drosophila

 描述(申请人提供)：在细胞水平上，代谢功能由TOR激酶调节。Tor作为细胞代谢状态的传感器，适当地调节代谢敏感的细胞过程，包括线粒体功能。然而，TOR与线粒体的联系机制目前尚不清楚。兰德实验室之前的工作表明，TOR抑制药物雷帕霉素在遗传上相同的果蝇品系中引起不同的线粒体反应，除了它们的线粒体基因组。这就做 利用基因组学和蛋白质组学以及对TOR信号通路已知成分的重点研究来阐明在该系统中介导雷帕霉素反应的因素网络。这种利用线粒体基因组变异的新方法将为深入了解TOR信号对线粒体功能的调节以及线粒体基因组在代谢信号中的作用提供依据。我的工作有可能揭示疾病和缩短寿命中代谢功能障碍的治疗目标。

 DESCRIPTION (provided by applicant): At the cellular level metabolic function is regulated by TOR kinase. TOR acts as a sensor of the cellular metabolic state and appropriately regulates metabolically-sensitive cellular processes including mitochondrial function. However, the mechanism connecting TOR to mitochondria is currently unknown. Previous work in the Rand laboratory revealed the TOR inhibitory drug rapamycin elicits different mitochondrial responses in Drosophila strains that are genetically identical except for their mitochondrial genomes. I will use genomics and proteomics as well as focused studies on known components of the TOR signaling pathway to elucidate the network of factors that mediate the rapamycin response in this system. This novel approach of using mitochondrial genome variants will provide insight into the regulation of mitochondrial function by TOR signaling and the role of the mitochondrial genome in metabolic signaling. My work has potential to reveal therapeutic targets for metabolic dysfunction in disease and shortened lifespan.