FIG. 1.

Enzymatic catalysis of oxidation of two polyunsaturated phospholipids, resulting in the signal formation. (A) 15-LO catalyzes oxidation of AA-PE to yield ferroptotic death signals. AA-OOH-PE is produced as the primary molecular product that can be subsequently reduced to respective hydroxy-derivatives or converted into epoxy-, oxo-, or oxidatively truncated electrophilic products with shortened side chains. (B) cyt c/CL peroxidase complex oxidizes linoleic acid residue in hetero-acylated CL to yield linoleoyl hydroperoxy-CL, hydroxy-, epoxy-, oxo-, or oxidatively truncated electrophilic products with shortened side chains. 15-LO, 15-lipoxygenases; AA-PE, arachidonoyl-phosphatidylethanolamine; AA-OOH-PE, 15-hydroperoxy-AA-PE; CL, cardiolipin; cyt c, cytochrome c. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars