On the origin of cysteamine-induced duodenal cytotoxicity and type II ferroptosis.

Cysteamine (CA) induces duodenal ulcers in rodents (Selye and Szabo, Nature 244:458–459, 1973). Cysteine (Cys), a precursor for the formation of CA (via catabolism of coenzyme A), does not cause lesions in the duodenum (Szabo et al., J Pharmacol Exp Ther 223:68–76, 1982). CA also has antimutagenic and anticancer pharmacology (Fujisawa et al., PLoS ONE 7, 2012; Lee, Adv Pharmacol Pharm Sci 2023:2419444, 2023). We propose a mechanism of CA-induced cell death dependent on oxygen and CA dioxygenase (ADO) that can explain the 50-year-old mystery as to why CA is, but Cys is not, ulcerogenic. Those cells expressing coenzyme A-catabolizing enzymes are subject to a unique type of oxygen- and enzyme-bound-Fe2+-dependent death, type II ferroptosis. [ABSTRACT FROM AUTHOR]