van Leyen K, Duvoisin R M, Engelhardt H, Wiedmann M
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature. 1998 Sep 24;395(6700):392-5. doi: 10.1038/26500.
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.
膜包被细胞器是真核细胞的一个典型特征，在特定细胞类型的分化过程中会消失，如网织红细胞（红细胞分化过程中的一个中间体）、眼晶状体的中央纤维细胞和角质形成细胞。这些细胞器的降解必须在激活时间和膜降解特异性方面受到严格调控。15-脂氧合酶（15-LOX）的表达在网织红细胞细胞器降解前即刻达到峰值。在此我们表明，15-LOX整合到各种细胞器的膜中，使蛋白质从细胞器腔中释放出来，并使蛋白酶能够接触到腔蛋白和整合膜蛋白。此外，通过避开质膜，15-LOX显示出对细胞器膜所需的特异性。因此，15-LOX的作用提供了一种可以解释自然降解过程的机制。我们发现在眼晶状体中脂氧合酶的表达仅限于细胞器发生降解的区域，这一发现支持了这一结论。
