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“Art is the elimination of the unnecessary: the (fat)al role of phospholipids.”

High fidelity of biological systems is frequently achieved by duplication of the essential intracellular machineries or, removal of the entire cell, which becomes unnecessary or even harmful in altered physiological environments. Carefully controlled removal of these cells, without damaging normal cells, requires precise signaling, and is critical to maintaining homeostasis. Phospholipids may act as effective signals for the removal of "the unnecessary” cells or organelles. This can be realized by collapse of inherent transmembrane asymmetry and the externalization of the signal on the membrane surface. Another mechanism is oxidative modification of polyunsaturated phospholipids leading to myriads of their oxidized molecular species. I will discuss how highly specific oxidation of cardiolipins by cytochrome c serves as a signal for mitochondria-dependent intrinsic apoptosis, while oxidation of phosphatidylethanolamines by lipoxygenases triggers ferroptotic cell death.