Abstract
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 the eye lens, and keratinocytes1. 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 degradation2. 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.
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Acknowledgements
We thank D. Smith and J. Olesker for assistance in writing the manuscript; T. Söllner, J. E. Rothman, P. Szabo, G. van Meer, D. Nikolov, A. Koff, G. Bacher, and members of the Wiedmann, Duvoisin and Rothman laboratories for discussions and comments; N. Min and L. Cohen-Gould for performing the initial immunohistochemistry and electron microscopy experiments. We thank P. Marks and R. Rifkind for suggesting the eye lens experiments. This work was supported by the Memorial Sloan-Kettering Cancer Center, a Fellowship by the Deutsche Forschungsgemeinschaft (to K.v.L.), and by the Samuel and May Rudin Foundation and a Tolly Vinik Pilot Grant Award (to R.M.D.).
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van Leyen, K., Duvoisin, R., Engelhardt, H. et al. A function for lipoxygenase in programmed organelle degradation. Nature 395, 392–395 (1998). https://doi.org/10.1038/26500
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DOI: https://doi.org/10.1038/26500
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