Novel role of peroxiredoxin 6 in ferroptosis: Bridging selenium transport with enzymatic functions

Ferroptosis, an iron dependent mode of cell death, is characterized by oxidative damage to cell membrane by uncontrolled lipid peroxidation. Prevention of lipid peroxide formation or its rapid neutralization is critical to avert ferroptosis. Selenoproteins such as glutathione peroxidase 4 (GPX4) and thioredoxin reductase 1 (TXNRD1) are critical enzymes which prevent ferroptosis. Peroxiredoxin 6 (PRDX6) is a lipid peroxide specific peroxidase enzyme with moonlighting functions that affect ferroptosis sensitivity in a multitude of ways. Further, it has recently been discovered that PRDX6 also acts as an intracellular carrier of selenium, allowing efficient utilization of organic and inorganic sources of selenium for synthesis of selenoproteins. Thus, PRDX6 can affect abundance and functionality of anti-ferroptotic selenoproteins GPX4 and TXNRD1. This review is focussed on understanding the different functions of PRDX6 in ferroptosis in light of its newly discovered role in selenoprotein synthesis.