Mediation of apoptosis by oxidized phospholipids

Free radical-mediated oxidation of (poly)unsaturated glycerophospholipids in membranes and lipoproteins leads to the formation of a plethora of products. Some of these oxidized phospholipids, especially the truncated forms, induce apoptosis depending on their chemical structure, concentration and cell type. Depending on the phospholipid and the cell type, two pathways have so far been identified for the intracellular transmission of the apoptotic signals. One pathway involves activation of acid sphingomyelinase, which gives rise to the formation of ceramide and is followed by phosphorylation of pro-apoptotic mitogen-activated protein kinases. Alternatively, oxidized phospholipids act directly on mitochondria leading to efflux of pro-apoptotic effectors in endothelial cells. During the execution of the apoptotic program additional oxidized phospholipids are generated. The apoptotic cascade itself leads to oxidation and exposure of e.g. membrane phosphatidylserine. Oxidized phospholipids on the outer leaflet of the plasma membrane can form surface lipid patterns that specifically bind to phagocytic cells, e.g. macrophages.In this manuscript we review the recent literature reporting on apoptosis-inducing glycerophospholipids. In addition, we describe the cellular processes that lead to phospholipid oxidation as part of the apoptotic mode of cell death and are likely to enhance the recognition of apoptotic cells by phagocytic macrophages.