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Thioredoxin, mitochondrial also known as thioredoxin-2 is a protein that in humans is encoded by the TXN2gene on chromosome 22. This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis.
This nuclear gene encodes a mitochondrial member of the thioredoxin family, a group of small multifunctional redox-active proteins. The encoded protein is ubiquitously expressed in all prokaryotic and eukaryotic organisms, but demonstrates especially high expression in tissues with heavy metabolic activity, including the stomach, testis, ovary, liver, heart, neurons, and adrenal gland. It may play important roles in the regulation of the mitochondrial membrane potential and in protection against oxidant-induced apoptosis. Specifically, the ability of TXN2 to reduce disulfide bonds enables the protein to regulate mitochondrial redox and, thus, the production of reactive oxygen species (ROS). By extension, downregulation of TXN2 can lead to increased ROS generation and cell death. The antiapoptotic function of TXN2 is attributed to its involvement in GSH-dependent mechanisms to scavenge ROS, or its interaction with, and thus regulation of, thiols in the mitochondrial permeability transition pore component adenine nucleotide translocator (ANT).
Overexpression of TXN2 was shown to have attenuatedhypoxia-induced HIF-1alpha accumulation, which is in direct opposition of the cytosolic TXN1, which enhanced HIF-1alpha levels. Moreover, although both TXN2 and TXN1 are able to reduceinsulin, TXN2 does not depend on the oxidative status of the protein for this activity, a quality which may contribute to their difference in function.
Clinical significance
It has been demonstrated that genetic polymorphisms in the TXN2 gene may be associated with the risk of spina bifida.
TXN2 is known to inhibit transforming growth factor (TGF)-β-stimulated ROS generation independent of Smad signaling. TGF-β is a pro-oncogeniccytokine that induces epithelial–mesenchymal transition (EMT), which is a crucial event in metastatic progression. In particular, TXN2 inhibits TGF-β-mediated induction of HMGA2, a central EMT mediator, and fibronectin, an EMT marker.
Ishikawa F, Kaneko E, Sugimoto T, Ishijima T, Wakamatsu M, Yuasa A, Sampei R, Mori K, Nose K, Shibanuma M (Jan 2014). "A mitochondrial thioredoxin-sensitive mechanism regulates TGF-β-mediated gene expression associated with epithelial-mesenchymal transition". Biochemical and Biophysical Research Communications. 443 (3): 821–7. doi:10.1016/j.bbrc.2013.12.050. PMID24342608.
Further reading
Wang Z, Zhang H, Li XF, Le XC (2007). "Study of interactions between arsenicals and thioredoxins (human and E. coli) using mass spectrometry". Rapid Communications in Mass Spectrometry. 21 (22): 3658–66. Bibcode:2007RCMS...21.3658W. doi:10.1002/rcm.3263. PMID17939155.
Zhang H, Go YM, Jones DP (Sep 2007). "Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress". Archives of Biochemistry and Biophysics. 465 (1): 119–26. doi:10.1016/j.abb.2007.05.001. PMID17548047.
