Caenorhabditis elegans pathways that surveil and defend mitochondria.
Caenorhabditis elegans pathways that surveil and defend mitochondria.
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线粒体功能受到代谢的有毒副产物以及病原体攻击的挑战。秀丽隐杆线虫通常通过激活线粒体修复、药物解毒和病原体反应途径来响应线粒体功能障碍。从全基因组RNAi筛选中，我们鉴定了45个C.这些基因是在药物或遗传破坏抑制线粒体功能后上调解毒、病原体反应和线粒体修复途径所需的。神经酰胺生物合成缺陷的动物缺乏线粒体监视，并且添加特定的神经酰胺可以挽救监视缺陷。神经酰胺还可以挽救其他基因失活的线粒体监视缺陷，将这些基因活动定位在神经酰胺上游。通过RNAi或他汀类药物抑制甲羟戊酸途径也会破坏线粒体监视。C.生长具有来自其自然栖息地的显著比例的细菌物种的秀丽线虫引起线粒体功能障碍。其他细菌种类抑制C.线虫对线粒体毒素的防御反应，揭示了动物防御的细菌对策。
Mitochondrial function is challenged by toxic byproducts of metabolism as well as by pathogen attack,. Caenorhabditis elegans normally responds to mitochondrial dysfunction with activation of mitochondrial repair, drug detoxification, and pathogen-response pathways. From a genome-wide RNAi screen, we identified 45 C. elegans genes that are required to upregulate detoxification, pathogen-response, and mitochondrial repair pathways after inhibition of mitochondrial function by drugs 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 inactivations, 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 defense responses to a mitochondrial toxin, revealing bacterial countermeasures to animal defense.
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DOI：
10.1016/j.bbamcr.2012.02.019
发表时间：
2013-02
影响因子：
5.1
作者：
Pellegrino, Mark W.;Nargund, Amrita M.;Haynes, Cole M.
通讯作者：
Haynes, Cole M.
影响因子：
64.5
作者：
Melo JA;Ruvkun G
通讯作者：
Ruvkun G
影响因子：
11.8
作者：
Haynes, Cole M.;Petrova, Kseniya;Ron, David
通讯作者：
Ron, David
影响因子：
64.5
作者：
Durieux J;Wolff S;Dillin A
通讯作者：
Dillin A
影响因子：
14.8
作者：
Sentelle, R. David;Senkal, Can E.;Jiang, Wenhui;Ponnusamy, Suriyan;Gencer, Salih;Selvam, Shanmugam Panneer;Ramshesh, Venkat K.;Peterson, Yuri K.;Lemasters, John J.;Szulc, Zdzislaw M.;Bielawski, Jacek;Ogretmen, Besim
通讯作者：
Ogretmen, Besim