Glutaredoxin (Grx)

Glutaredoxin is a small redox enzyme and member of the thioredoxin protein family, present in nearly all organisms from bacteria to humans[1][2][3][4]. It contains a catalytic site typically composed of a cysteine pair (Cys-X-X-Cys motif), enabling it to catalyze the reversible reduction of protein or substrate disulfides using glutathione as a cofactor. Uniquely, glutaredoxins use the glutathione system—specifically, reduced glutathione (GSH) as an electron donor and glutathione reductase for GSH recycling—instead of a dedicated reductase protein[1][3][5]. Their primary roles include maintenance of cellular redox homeostasis, defense against oxidative stress, and regulation of protein function via reversible protein S-glutathionylation and deglutathionylation, crucial in a wide range of physiological and pathological contexts, from DNA synthesis (as hydrogen donor for ribonucleotide reductase) to the assembly and transfer of iron-sulfur clusters important for mitochondrial function[2][3][4]. Glutaredoxins have distinct isoforms (e.g. GLRX1, GLRX2, GLRX3, GLRX5) with specialized functions and localizations in cells[3][7]. Dysregulation or mutation in glutaredoxins has been implicated in cancer, neurodegeneration, cardiovascular conditions, and immune disorders, supporting ongoing interest in the class as putative therapeutic targets and biomarkers[2][3][4].

Other names

ThioltransferaseGrxGlutaredoxin-1 (GLRX1)Glutaredoxin-2 (GLRX2)Glutaredoxin-3 (GLRX3)Glutaredoxin-5 (GLRX5)Thiol-disulfide oxidoreductase

Catalysis of glutathione-dependent reduction of disulfides and mixed disulfides, regulating cellular redox state and modulating protein function via reversible glutathionylation[2][3].