Caenorhabditis elegans pathways that surveil and defend mitochondria

摘要

Mitochondrial function is challenged by toxic by-products of meta-bolism as well as by pathogen attack. Caenorhabditis elegans normally responds to mitochondrial dysfunction with activation of mitochondrial-repair, drug-detoxification and pathogen-response pathways. Here, from a genome-wide RNA interference (RNAi) screen, we identified 45 C. elegans genes that are required to upreg-ulate detoxification, pathogen-response and mitochondrial-repair pathways after inhibition of mitochondrial function by drug-induced or genetic disruption. Animals defective in ceramide biosynthesis are deficient in mitochondrial surveillance, and addition of particular ceramides can rescue the surveillance defects. Ceramide can also rescue the mitochondrial surveillance defects of other gene inactiva-tions, mapping these gene activities upstream of ceramide. Inhibition of the mevalonate pathway, either by RNAi or statin drugs, also disrupts mitochondrial surveillance. Growth of C.elegans with a significant fraction of bacterial species from their natural habitat causes mitochondrial dysfunction. Other bacterial species inhibit C. elegans defence responses to a mitochondrial toxin, revealing bacterial coun-termeasures to animal defence.%线粒体（通过呼吸产生能量的细胞器）受损会触发各种保护性程序，但我们对监测线粒体功能和将其耦合到保护措施的信号作用通道却知之甚少。通过对线虫进行全基因组RNA干涉筛选，Gary Ruvkun及同事识别出在线粒体受到由药物介导的基因破坏之后在上调保护性通道中所涉及的45个基因。受这些基因影响、与监测相关的通道包括信号作用脂质“神经酰胺”的生物合成以及甲羟戊酸通道（该通道被能降低胆固醇的药物“斯达汀”抑制）。