The Thiol-Redox Biochemistry of Trypanosomatids: A New Perspective Based on Known and New Actors

Maintaining thiol redox homeostasis is key for cell viability and development. Therefore, all organisms are equipped with redox systems conformed by redox-active proteins and low-molecular-weight thiols that facilitate target-specific delivery of electrons from NADPH to different (macro)molecules. Trypanosomatids are early branching single-cell eukaryotes harboring a unique thiol-redox system centered on the use of trypanothione (bis-glutathionylspermidine) as a low-molecular-weight thiol-redox cofactor. The irruption of trypanothione in these organisms acted as a major and positive selective pressure that shaped their redox biochemistry. The most radical changes involved the loss of otherwise highly conserved and indispensable glutathione reductase and thioredoxin reductase genes and the concomitant assignment of secondary roles to the related redoxins (glutaredoxins and thioredoxins). Here, we revise the state-of-the-art on the field and provide new research perspectives based on the identification of novel members of the thioredoxin-fold family.