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Caenorhabditis elegans pathways that surveil and defend mitochondria.

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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4102179 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Caenorhabditis elegans pathways that surveil and defend mitochondria.

Liu Ying Y Samuel Buck S BS Breen Peter C PC Ruvkun Gary G

Nature 20140402 7496

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 ...[more]

PMID: 24695221

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Project description:In Caenorhabditis elegans, the binding of Piwi protein to a non-coding RNA form, called piRNA, has been found to be important to both reproductive and aging processes. As the biosynthesis of piRNA is modulated by mitochondrial function, it is likely that the interaction between mitochondrial function and piRNA expression plays an unknown, yet important, role in reproductive and aging processes because both processes are known to be affected by declines in mitochondrial quality and activity. While the relationship between reproduction and longevity is not characterized in full, the optimality theory of aging and the disposable soma theory suggest that a trade-off between energy and resources is needed for reproductive and aging maintenance. In this study, the influence of mitochondrial variations, via a respiratory chain complex IV (COX1) polymorphism, on piRNA expression was examined in relation to the reproductive and aging outcomes of C. elegans. The COX1 polymorphism in mitochondria was found to affect the number of piRNAs expressed, the development of germ cells, and the length of the lifespan of the nematodes. Interestingly, more than two-thirds of the piRNA expression changes associated with the mitochondrial variation were found to also be affected by age. A gene ontology analysis of the altered piRNA species found that the piRNAs affected by mitochondrial variation and age were linked to genes known to have roles in reproductive and developmental function. Moreover, a piRNA-lncRNA-mRNA regulatory network based on the differential expression patterns of piRNA related to the mitochondrial variation was constructed to further identify potential gene targets with functional interactions. Similarly, this network identified genes involved in reproduction, development, and aging processes. These findings provide new insight into understanding how mitochondrial variations may regulate piRNA expression and may influence the underlying molecular mechanisms that affect reproduction and aging.

Dataset Information

Caenorhabditis elegans pathways that surveil and defend mitochondria.

Publications

Caenorhabditis elegans pathways that surveil and defend mitochondria.

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