Hyperoxidized PRDX3 as a specific ferroptosis marker

<正>The lack of a reliable and specific marker for ferroptosis has hindered the advancement of treatments related to this cell death mechanism toward clinical application. A recent study published in Molecular Cell has identified hyperoxidized peroxiredoxin 3(PRDX3) as a promising marker for ferroptosis, opening up new avenues for monitoring and targeting ferroptosis in disease treatment.Ferroptosis represents a form of regulated cell death driven by disturbed iron metabolism and excessive accumulation of detrimental lipid peroxides on cellular membranes [1]. It is distinctive from other forms of regulated cell death, such as apoptosis, necroptosis, and pyroptosis, through its unique morphological, biochemical, and genetic characteristics [2]. To safeguard against the adverse effects of lipid peroxides, mammalian cells have evolved robust antioxidant systems. The principal defense mechanism against ferroptosis is the solute carrier family 7 member 11(SLC7A11)-cyst(e)ine-glutathione(GSH)-glutathione peroxidase 4(GPX4) axis(Fig. 1) [3]. Within this signaling axis, SLC7A11 plays a pivotal role in importing extracellular cystine, which is subsequently reduced to cysteine to synthesize intracellular GSH [4]. GPX4, acting as a phospholipid hydroperoxidase, utilizes GSH as a cofactor to catalyze the conversion of lipid peroxides into nontoxic lipid alcohols, effectively suppressing ferroptosis(Fig. 1) [3].