Caenorhabditis elegans pathways that surveil and defend mitochondria
| Autor: | Ying Liu, Gary Ruvkun, Buck S. Samuel, Peter C. Breen |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Ceramide
Serine C-Palmitoyltransferase Mevalonic Acid Mevalonic acid Biology Mitochondrion Ceramides chemistry.chemical_compound RNA interference Mitochondrial unfolded protein response Animals Homeostasis Caenorhabditis elegans Caenorhabditis elegans Proteins Gene Genetics Genome Multidisciplinary biology.organism_classification Mitochondria chemistry Inactivation Metabolic RNA Interference Mevalonate pathway Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| Zdroj: | Nature. 508:406-410 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature13204 |
| Popis: | A genome-wide RNA interference screen in Caenorhabditis elegans identifies 45 genes with roles in protective pathways following drug- and genetic-disruption-induced mitochondrial inhibition. Damage to mitochondria, the cellular organelles that generate energy through respiration, triggers various protective programs, but little is known about the signalling pathways that monitor mitochondrial function and couple it to protective measures. Through a genome-wide RNA interference screen in the nematode Caenorhabditis elegans, Gary Ruvkun and colleagues identify 45 genes involved in upregulating the protective pathways following drug-mediated and genetic disruptions to mitochondria. Pathways affected by these genes and linked to surveillance include biosynthesis of the signalling lipid ceramide, and the mevalonate pathway (inhibited by the cholesterol-lowering statins). Mitochondrial function is challenged by toxic by-products of metabolism as well as by pathogen attack1,2. Caenorhabditis elegans normally responds to mitochondrial dysfunction with activation of mitochondrial-repair, drug-detoxification and pathogen-response pathways1,2,3,4,5,6,7. 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. |
| Databáze: | OpenAIRE |
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