Grx1

Grx1, or glutaredoxin-1, is a small cytosolic enzyme that belongs to the glutaredoxin family of thiol-disulfide oxidoreductases. It participates in cellular redox control by catalyzing reactions that rely on glutathione (GSH), helping to maintain redox balance and modulate signaling processes. Grx1 is conserved across a wide range of organisms, including bacteria, yeast, plants, and animals, and in humans it is encoded by the GLRX gene.

Grx1 is a dithiol glutaredoxin with a thioredoxin-like fold and a catalytic CPYC active-site motif. It facilitates the reduction of protein disulfides and the deglutathionylation of S-glutathionylated cysteine residues. The catalytic cycle involves the formation of a Grx1-substrate mixed disulfide and regeneration of the active site by GSH, releasing GSSG and restoring Grx1 to its reduced form.

In cells, Grx1 contributes to redox homeostasis and redox signaling by reversing glutathionylation on a variety of substrates, thereby influencing the activity, stability, and interactions of enzymes and transcription factors. It is predominantly localized in the cytosol, with some presence in the nucleus, and participates in broader networks of redox regulation through interactions with numerous partner proteins.

Regulation of Grx1 occurs in response to cellular redox state. Under oxidative stress, Grx1 can become oxidized and must be reduced to continue functioning, and its expression and activity can be modulated by cellular signaling pathways. Dysregulation of Grx1 activity has been linked to oxidative stress-related conditions, and ongoing research explores its roles in aging, cancer, and neurodegenerative diseases, as well as its potential as a therapeutic target or biomarker.