Fatty acid signals as quorum sensing regulators of mitochondrial biogenesis

线粒体的数量在细胞内受到非常严格的调控。发展对线粒体数量和新陈代谢调节的理解在人类健康和疾病的几乎所有领域都是重要的。该建议的目的是研究核/线粒体通讯现象及其在脑内的作用。 线粒体数量的调节。工作假说是，线粒体进化出了与其细菌祖先的群体感应通路非常相似的途径，以传达增加或减少细胞中线粒体含量的需要。三个标准将被用来确定线粒体中是否存在群体感应类型的信号通路。第一个是存在类似于仲裁感知的 线粒体产生和释放的信号分子。这种分子将使用类似于在细菌中分离群体感应分子的方法进行检测。第二个标准是线粒体衍生分子驱动线粒体生物发生相关分子转录的能力。第三个标准是线粒体衍生分子在整个细胞系统中引起或抑制线粒体生物发生的能力。线粒体包含类似于细菌群体感应的途径的发现将使我们能够更全面地了解细胞中线粒体数量和新陈代谢的调节，并最终可能导致更好地了解线粒体数量重要的多种人类疾病，包括但不限于癌症、衰老、基于线粒体DNA的疾病、糖尿病和肥胖症。此外，识别线粒体生物发生的基于脂质的信号将为这些疾病的药物干预打开大门。

Mitochondrial number is very tightly regulated within the cell. Developing an understanding of regulation of mitochondrial number and metabolism is important in almost every area of human health and disease. The goal of this proposal is to investigate the phenomenon of nuclear/mitochondrial communication and its role in regulation of mitochondrial number. The working hypothesis is that mitochondria have evolved pathways very similar to the quorum sensing pathways of their bacterial ancestors to communicate the need to increase or decrease mitochondrial content in the cell. Three criteria will used to determine if a quorum sensing type signaling pathway has been conserved in mitochondria. The first is the presence of a quorum sensing-like signaling molecule produced and released from the mitochondria. This molecule will be detected using methods similar to those established for isolating quorum sensing molecules in bacteria. The second criterion is the ability of mitochondrially derived molecules to drive transcription of mitochondrial biogenesis related molecules. The third criterion is the ability of the mitochondrially derived molecules to cause or suppress mitochondrial biogenesis in a whole cell system. The finding that mitochondria contain a pathway similar to bacterial quorum sensing would allow a more complete understanding of the regulation of mitochondrial number and metabolism in the cell, and could ultimately lead to better understanding of a multitude of human conditions where mitochondrial number is important, including but not limited to cancer, aging, mitochondrial DNA based disease, diabetes, and obesity. In addition, the identification of a lipid based signal for mitochondrial biogenesis would open the door for pharmacological intervention in these diseases.