Mechanisms of defense against products of cysteine catabolism in the nematode Caenorhabditis elegans

Leonid Livshits, Arijit Kumar Chatterjee, Netanel Karbian, Rachel Abergel, Zohar Abergel, Einav Gross*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Cysteine catabolism presents cells with a double-edged sword. On the one hand, cysteine degradation provides cells with essential molecules such as taurine and sulfide. The formation of sulfide in cells is thought to regulate important and diverse physiological processes including blood circulation, synaptic activity and inflammation. On the other hand, the catabolism of cysteine by gut microbiota can release high levels of sulfide that may underlie the development or relapse of ulcerative colitis, an inflammatory bowel disease affecting millions of people worldwide. Here, we have used the nematode C. elegans to explore how cells tolerate high levels of sulfide produced by cysteine degradation in bacteria. We have identified mutations in genes coding for thioredoxin family proteins, mitochondrial proteins, and collagens that confer tolerance to sulfide toxicity. Exposure to sulfide induces the unfolded protein response in the endoplasmic reticulum and mitochondria. Moreover, our results suggest that sulfide toxicity is mediated by reactive oxygen species (ROS). Indeed, pre-treatment of worms with antioxidants increases their tolerance to sulfide toxicity. Intriguingly, sub-toxic levels of the superoxide generator paraquat can also increase the tolerance of worms to sulfide. Therefore, it appears that activation of ROS detoxification pathway prior to the exposure to sulfide, can increase the tolerance to sulfide toxicity. Our results suggest that these detoxification pathways are mediated by the hypoxia inducible factor HIF-1. Finally, we show that sulfide resistance varies among wild C. elegans and other nematode species, suggesting that tolerance to sulfide was naturally selected in certain habitats.

Original languageAmerican English
Pages (from-to)346-359
Number of pages14
JournalFree Radical Biology and Medicine
Volume104
DOIs
StatePublished - 1 Mar 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

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