A function for lipoxygenase in programmed organelle degradation.
Membrane-enclosed organelles, a defining characteristic of eukaryotic cells, are lost during differentiation of specific cell types such as reticulocytes (an intermediate in differentiation of erythrocytes), central fibre cells of the eye lens, and keratinocytes. The degradation of these organelles must be tightly regulated with respect to both the time of activation and the specificity of membrane degradation. The expression of 15-lipoxygenase (15-LOX) peaks in reticulocytes immediately before organelle degradation. Here we show that 15-LOX integrates into the membranes of various organelles, allowing release of proteins from the organelle lumen and access of proteases to both lumenal and integral membrane proteins. In addition, by sparing the plasma membrane, 15-LOX shows the required specificity for organellar membranes. Thus, the action of 15-LOX provides a mechanism by which the natural degradation process can be explained. This conclusion is supported by our finding that lipoxygenase expression in the eye lens is restricted to the region at which organelle degradation occurs.
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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van Leyen
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RM
Duvoisin
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H
Engelhardt
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M
Wiedmann
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007425:Intracellular Membranes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D007908:Lens, Crystalline / Q000166:cytology; D008081:Liposomes; D016859:Lipoxygenase Inhibitors; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D015388:Organelles / Q000201:enzymology* / Q000502:physiology*; D010539:Permeability; D011435:Propyl Gallate / Q000494:pharmacology; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology / Q000502:physiology; D012995:Solubility
D004791:Enzyme Inhibitors; D008081:Liposomes; D016859:Lipoxygenase Inhibitors; D008563:Membrane Lipids; D008565:Membrane Proteins; D011435:Propyl Gallate; D001093:Arachidonate 15-Lipoxygenase