Glutathione (GSH) and GSH-dependent enzymes play a key role in cellular detoxification processes that enable organism to cope with various internal and environmental stressors. However, it is often not clear, which components of the complex GSH-metabolism are required for tolerance towards a certain stressor. To address this question, a small scale RNAi-screen was carried out in Caenorhabditis elegans where GSH-related genes were systematically knocked down and worms were subsequently analysed for their survival rate under sub-lethal concentrations of arsenite and the redox cycler juglone. While the knockdown of γ-glutamylcysteine synthetase led to a diminished survival rate under arsenite stress conditions, GSR-1 (glutathione reductase) was shown to be essential for survival under juglone stress conditions. gsr-1 is the sole GSR encoding gene found in C. elegans. Knockdown of GSR-1 hardly affected total glutathione levels nor reduced glutathione/glutathione disulphide (GSH/GSSG) ratio under normal laboratory conditions. Nevertheless, when GSSG recycling was impaired by gsr-1(RNAi), GSH synthesis was induced, but not vice versa. Moreover, the impact of GSSG recycling was potentiated under oxidative stress conditions, explaining the enormous effect gsr-1(RNAi) knockdown had on juglone tolerance. Accordingly, overexpression of GSR-1 was capable of increasing stress tolerance. Furthermore, expression levels of SKN-1-regulated GSR-1 also affected life span of C. elegans, emphasising the crucial role the GSH redox state plays in both processes.

Apicomplexan parasites cause infectious diseases that are either a severe public health problem or an economic burden. In this paper we will shed light on how oxidative stress can influence the host-pathogen relationship by focusing on three major diseases: babesiosis, coccidiosis, and toxoplasmosis.

Background:The novel ubiquitin-like modifier (UBL) Ufm1 has essential functions in mammalian embryonic development. Results: The Ufm1 cascade in Caenorhabditis elegans is required for normal growth and development and is involved in cellular stress response. Conclusions: The C. elegans Ufm1 cascade is an antagonist of the unfolded protein response. Significance: The C. elegans Ufm1 cascade offers a unique opportunity to understand the fundamentals underlining this UBL.

Background: Ornithine decarboxylase degradation by the proteasome is promoted by antizyme. Results: A novel reporter gene approach was established to monitor translational frameshifting of C. elegans antizyme in vivo. Conclusion: Induction of antizyme-frameshifting also occurs under stressful conditions, even in the absence of polyamine synthesis and independent of polyamine concentrations. Significance: A polyamine-independent regulation of frameshifting under stressful conditions is proposed.