Oxidative stress, selenium redox systems including gpx/txnrd families

Abstract

A third of the mammalian selenoprotein repertoire accounts for the two main cellular redox systems in mammals, i.e., the glutathione- and thioredoxin-dependent systems. All three thioredoxin reductases contain selenocysteine as their penultimate amino acid and keep thioredoxins in their reduced, active state. Cytosolic thioredoxin reductase (TXNRD1) and mitochondrial thioredoxin reductase (TXNRD2) are directly involved in cell proliferation and cell protection of somatic cells, respectively, whereas thioredoxin-glutathione reductase (TXNRD3) contributes to sperm development. Five out of eight glutathione peroxidases (GPX) are selenoproteins in humans and are part of antioxidant network by keeping the levels of cellular peroxides in check. Among these, glutathione peroxidase 4 (GPX4) is unusual as it confers a moonlighting and essential function in sperm development because of its promiscuity towards reducing substrates. Moreover, due to its unique activity to efficiently reduce phospholipid hydroperoxides, GPX4 has emerged as one of the most important selenoproteins in mammals. In fact, we and others found that GPX4 is the key regulator of a recently described form of regulated necrotic cell death, called ferroptosis. Hence, this chapter aims at illuminating the importance of the main mammalian antioxidant systems in health and disease.