Physiological and modulatory role of thioredoxins in the cellular function

Thioredoxins (TRXs) are a class of ubiquitous and multifunctional protein. Mammal cells present three isoforms: a cytosolic and extracellular called thioredoxin 1 (TRX1), a mitochondrial (TRX2), and one specific in spermatozoids (TRX3). Besides, a truncated form called TRX80 exists, which results from the post-translational cleavage performed on TRX1. TRXs’ main function is to maintain the reduction–oxidation homeostasis of the cell, reducing the proteins through a thiol-disulfide exchange that depends on two cysteines located in the active site of the protein (Cys32-X-X-Cys35 in humans). In addition, TRX1 performs S-nitrosylation, a post-translational modification of proteins that depends on cysteines of its C-terminal region (Cys62, Cys69, and Cys73 in human TRX1). These modifications allow the TRXs to modulate the protein function and participate in regulating diverse cellular processes, such as oxidative stress, transcription, signaling cascades, apoptosis, inflammation, and immunologic response. This points out the crucial relevance of TRXs for cell function, signaling it as a strategic target for the treatment of many diseases and its possible use as a therapeutic factor.