Distal Mitochondrial Signaling in a Multicellular Organism

项目摘要 线粒体功能障碍是几乎所有年龄起病的神经退行性疾病的主要后果，并且 可能是接触到即使是轻微水平的广泛环境毒素的后果。令人惊讶的是， 申请人的实验室发现，一种细胞类型的线粒体压力可以传递到远端 没有经历过线粒体应激的细胞类型。利用线虫C. 在神经系统中驱动ETC复合体IV的一个亚单位的dsRNA表达的优雅动物，它有 已有研究表明，神经元线粒体应激可传递到远端细胞，如肠道。这个 神经系统传递这种轻微压力的能力会导致延长寿命和延长小鼠的存活率 整个动物。拟议研究的目标是确定这种信号的来源和性质 机制。

Project Summary Mitochondrial dysfunction is a primary consequence of nearly all age-onset neurodegenerative diseases, and can be the consequence of exposure to even mild levels of a wide-range of environmental toxins. Surprisingly, the applicant's lab has uncovered that mitochondrial stress in one cell type can be communicated to a distal cell type that has not undergone mitochondrial stress. Using issue specific promoters in the nematode C. elegans that drive expression of dsRNA of a subunit of complex IV of the ETC in the nervous system, it has been shown that neuronal mitochondrial stress can be communicated to distal cells, such as the intestine. The ability of the nervous system to communicate this mild stress results in increased longevity and survival of the entire animal. The goal of the proposed studies is to identify the source and nature of this signaling mechanism.