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性神经退行性疾病的主要后果，并且可能是暴露于各种环境毒素的结果，即使是轻度水平。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应激可以传递给未经历线粒体应激的远端细胞类型。利用线虫的组织特异性启动子驱动神经系统ETC复合体IV亚基的dsRNA的表达，研究表明神经元线粒体应激可以传递到远端细胞，如肠。神经系统传递这种轻微压力的能力增加了整个动物的寿命和存活率。提出的研究的目的是确定这种信号机制的来源和性质。

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.