Sergey Korolev, Ph.D., recently published a paper with collaborators at the University of Pittsburgh. The paper in Nature Chemical Biology is entitled “Phospholipase iPLA2β averts ferroptosis by eliminating a redox lipid death signal” and shows that phospholipase A2β is a new ferroptosis regulator due to its ability to hydrolyze peroxidized phospholipids.
Ferroptosis results in accumulation of discoordinated iron, thiols, and lipids, resulting in the ferroptotic 15-HpETE-PE death signal. Hydrolization of 15-HpETE-PE by iPLA2β averts ferroptosis. Previous studies have shown that PLA2G6 mutations result in neurodegeneration. Therefore, Parkinson’s disease fibroblasts were analyzed and found to have decreased 15-HpETE-PE-hydrolyzing activity. In addition, elevated 15-HpETE-PE levels and decreased iPLA2β levels were found in parkisonian rat brains. Taken together, these results indicate a role of iPLA2β in regulation of ferroptosis and its mutation or loss may be a possible role in the pathogenesis of Parkinson’s disease.