Journal article

Publication year: 2014

Pages: 2923-2935

Journal: Antioxidants & Redox Signaling

Volume number: 20

Issue number: 18

ISSN: 1523-0864

eISSN: 1557-7716

Open access status: Green

DOI Link: https://doi.org/10.1089/ars.2013.5553

Publisher: Mary Ann Liebert

Abstract: 
Aims: Due to its life in different hosts and environments, the human malaria parasite Plasmodium falciparum is exposed to oxidative and nitrosative challenges. Nitric oxide (NO) and NO-derived reactive nitrogen species can constitute nitrosative stress and play a major role in NO-related signaling. However, the mode of action of NO and its targets in P. falciparum have hardly been characterized. Protein S-nitrosylation (SNO), a post-translational modification of protein cysteine thiols, has emerged as a principal mechanism by which NO exerts diverse biological effects. Despite its potential importance, SNO has hardly been studied in human malaria parasites. Using a biotin-switch approach coupled to mass spectrometry, we systemically studied SNO in P. falciparum cell extracts. Results: We identified 319 potential targets of SNO that are widely distributed throughout various cellular pathways. Glycolysis in the parasite was found to be a major target, with glyceraldehyde-3-phosphate dehydrogenase being strongly inhibited by S-nitrosylation of its active site cysteine. Furthermore, we show that P. falciparum thioredoxin 1 (PfTrx1) can be S-nitrosylated at its nonactive site cysteine (Cys43). Mechanistic studies indicate that PfTrx1 possesses both denitrosylating and transnitrosylating activities mediated by its active site cysteines and Cys43, respectively. Innovation: This work provides first insights into the S-nitrosoproteome of P. falciparum and suggests that the malaria parasite employs the thioredoxin system to deal with nitrosative challenges. Conclusion: Our results indicate that SNO may influence a variety of metabolic processes in P. falciparum and contribute to our understanding of NO-related signaling processes and cytotoxicity in the parasites.

Harvard Citation style: Wang, L., Delahunty, C., Prieto, J., Rahlfs, S., Jortzik, E., Yates, J., et al. (2014) Protein S-nitrosylation in Plasmodium falciparum, Antioxidants & Redox Signaling, 20(18), pp. 2923-2935. https://doi.org/10.1089/ars.2013.5553

APA Citation style: Wang, L., Delahunty, C., Prieto, J., Rahlfs, S., Jortzik, E., Yates, J., & Becker, K. (2014). Protein S-nitrosylation in Plasmodium falciparum. Antioxidants & Redox Signaling. 20(18), 2923-2935. https://doi.org/10.1089/ars.2013.5553