Distal Mitochondrial Signaling in a Multicellular Organism

描述（由申请人提供）：线粒体功能障碍是几乎所有年龄发作性神经退行性疾病的主要后果，并且可能是暴露于甚至轻度水平的广泛环境毒素的后果。令人惊讶的是，申请人的实验室已经发现，一种细胞类型中的线粒体应激可以传递到未经历线粒体应激的远端细胞类型。利用组织特异性启动子在线虫C.在神经系统中驱动ETC的复合物IV的亚基的dsRNA表达的线虫中，已经显示神经元线粒体应激可以传递到远端细胞，例如肠。神经系统传递这种轻微压力的能力会增加整个动物的寿命和存活率。拟议研究的目标是确定这种信号传导机制的来源和性质。

DESCRIPTION (provided by applicant): 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 tissue 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.