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Journal articles
Trypanothione: a unique bis-glutathionyl derivative in trypanosomatids.
Abstract : BACKGROUND: Trypanosomatids are early-diverging eukaryotes devoid of the major disulfide reductases - glutathione reductase and thioredoxin reductase - that control thiol-redox homeostasis in most organisms. These protozoans have evolved a unique thiol-redox system centered on trypanothione, a bis-glutathionyl conjugate of spermidine. Notably, the trypanothione system is capable to sustain several cellular functions mediated by thiol-dependent (redox) processes. SCOPE OF REVIEW: This review provides a summary of some historical and evolutionary aspects related to the discovery and appearance of trypanothione in trypanosomatids. It also addresses trypanothione's biosynthesis, physicochemical properties and reactivity towards biologically-relevant oxidants as well as its participation as a cofactor for metal binding. In addition, the role of the second most abundant thiol of trypanosomatids, glutathione, is revisited in light of the putative glutathione-dependent activities identified in these organisms. MAJOR CONCLUSIONS: Based on biochemical and genome data, the occurrence of a thiol-redox system that is strictly dependent on trypanothione appears to be a feature unique to the order Kinetoplastida. The properties of trypanothione, a dithiol, are the basis for its unique reactivity towards a wide diversity of oxidized and/or electrophilic moieties in proteins and low molecular weight compounds from endogenous or exogenous sources. Novel functions have emerged for trypanothione as a potential cofactor in iron metabolism. GENERAL SIGNIFICANCE: The minimalist thiol-redox system, developed by trypanosomatids, is an example of metabolic fitness driven by the remarkable physicochemical properties of a glutathione derivative. From a pharmacological point of view, such specialization is the Achilles' heel of these ancient and deadly parasites. This article is part of a Special Issue entitled Cellular functions of glutathione.
Cited literature [266 references]
https://hal-riip.archives-ouvertes.fr/pasteur-00847176
Contributor : Mariella Botta Connect in order to contact the contributor
Submitted on : Monday, July 22, 2013 - 8:45:29 PM
Last modification on : Tuesday, January 18, 2022 - 2:50:07 PM
Long-term archiving on: : Wednesday, April 5, 2017 - 4:12:20 PM
Contributor : Mariella Botta Connect in order to contact the contributor
Submitted on : Monday, July 22, 2013 - 8:45:29 PM
Last modification on : Tuesday, January 18, 2022 - 2:50:07 PM
Long-term archiving on: : Wednesday, April 5, 2017 - 4:12:20 PM