Lange Yvonne, Ye Jin, Steck Theodore L
Department of Pathology, Rush University Medical Center, Chicago, Illinois, United States of America.
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, United States of America.
PLoS One. 2014 Jul 11;9(7):e98482. doi: 10.1371/journal.pone.0098482. eCollection 2014.
It has been shown that modestly increasing plasma membrane cholesterol beyond its physiological set point greatly increases the endoplasmic reticulum and mitochondrial pools, thereby eliciting manifold feedback responses that return cell cholesterol to its resting state. The question arises whether this homeostatic mechanism reflects the targeting of cell surface cholesterol to specific intracellular sites or its general equilibration among the organelles. We now show that human fibroblast cholesterol can be increased as much as two-fold from 2-hydroxypropyl-β-cyclodextrin without changing the size of the cell surface pool. Rather, essentially all of the added cholesterol disperses rapidly among cytoplasmic membranes, increasing their overall cholesterol content by as much as five-fold. We conclude that the level of plasma membrane cholesterol is normally at capacity and that even small increments above this physiological set point redistribute essentially entirely to intracellular membranes, perhaps down their chemical activity gradients.
研究表明，适度提高质膜胆固醇水平使其超出生理设定点，会大幅增加内质网和线粒体中的胆固醇池，从而引发多种反馈反应，使细胞胆固醇恢复到静息状态。由此产生的问题是，这种稳态机制反映的是细胞表面胆固醇靶向特定的细胞内位点，还是其在细胞器之间的普遍平衡。我们现在表明，从2-羟丙基-β-环糊精中提取的人类成纤维细胞胆固醇可以增加两倍，而不会改变细胞表面胆固醇池的大小。相反，基本上所有添加的胆固醇都迅速分散在细胞质膜中，使其总胆固醇含量增加了多达五倍。我们得出结论，质膜胆固醇水平通常已达极限，即使略高于此生理设定点的小幅度增加，也基本上完全重新分布到细胞内膜，可能是沿着其化学活性梯度进行的。
