RRC ID 45793
Author Liu Y, Samuel BS, Breen PC, Ruvkun G.
Title Caenorhabditis elegans pathways that surveil and defend mitochondria.
Journal 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.
Volume 508(7496)
Pages 406-10
Published 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
Times Cited 136
C.elegans tm4525