Thioredoxin-2 (TRX2) (TRX2)

Thioredoxin-2 (Trx2) is a mitochondrial-specific oxidoreductase that plays a critical role in maintaining cellular redox homeostasis and regulating apoptosis. It functions as a key component of the mitochondrial thioredoxin system, where it reduces oxidized proteins and scavenges reactive oxygen species (ROS) to prevent oxidative damage (UniProt P32234). By binding to and inhibiting apoptosis signal-regulating kinase 1 (ASK1), Trx2 acts as a negative regulator of mitochondrial-mediated cell death pathways (PubMed: 11500483). In disease contexts, particularly cancer, Trx2 is often overexpressed to support survival under high oxidative stress, making it an attractive therapeutic target. Targeted inhibition of Trx2 or its reductase (TrxR2) leads to excessive ROS accumulation, activation of ASK1, and subsequent induction of apoptosis in malignant cells (PubMed: 25103494). Current pharmacological strategies include small molecule inhibitors and gold-based compounds like auranofin that disrupt the redox-cycling capacity of the Trx2 system.

Other names

TXN2Mitochondrial thioredoxinMTRXTRX-2Thioredoxin mitochondrial

Inhibition of the thioredoxin system, primarily through the inhibition of thioredoxin reductase 2 (TrxR2) or direct binding to Trx2, leads to increased mitochondrial reactive oxygen species (ROS), the release of Apoptosis Signal-regulating Kinase 1 (ASK1), and subsequent induction of the intrinsic apoptotic pathway.