RRC ID 45793
著者 Liu Y, Samuel BS, Breen PC, Ruvkun G.
タイトル Caenorhabditis elegans pathways that surveil and defend mitochondria.
ジャーナル Nature
Abstract Mitochondrial function is challenged by toxic by-products 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. Here, from a genome-wide RNA interference (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 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 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 defence responses to a mitochondrial toxin, revealing bacterial countermeasures to animal defence.
巻・号 508(7496)
ページ 406-10
公開日 2014-4-17
DOI 10.1038/nature13204
PII nature13204
PMID 24695221
PMC PMC4102179
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Ceramides / biosynthesis Genome / genetics Homeostasis Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology Inactivation, Metabolic / genetics Mevalonic Acid / metabolism Mitochondria / drug effects Mitochondria / genetics Mitochondria / metabolism* Mitochondria / microbiology Mitochondria / pathology* RNA Interference Serine C-Palmitoyltransferase / genetics Serine C-Palmitoyltransferase / metabolism
IF 42.779
引用数 136
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm4525