Loss of membrane cholesterol influences lysosomal permeability to potassium ions and protons
Loss of membrane cholesterol influences lysosomal permeability to potassium ions and protons
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DOI：
10.1016/j.bbamem.2008.11.018
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发表时间：
2009-02-01
影响因子：
3.4
通讯作者：
Zhang, Guo-jiang
中科院分区：
文献类型：
--
作者：
Deng, Dong;Jiang, Nan;Zhang, Guo-jiang
胆固醇是溶酶体膜的重要组成部分。本文研究了膜胆固醇对大鼠肝溶酶体K ~+和H ~+通透性及细胞器稳定性的影响。通过测量溶酶体β-氨基己糖苷酶自由活性、膜电位、膜流动性、溶酶体内pH和溶酶体质子泄漏，我们确定甲基-β-环糊精（M β CD）引起的膜胆固醇损失可增加溶酶体对钾离子和质子的渗透性，并破坏溶酶体膜。结果，钾离子通过K+/H+交换进入溶酶体，产生跨膜渗透压不平衡并使溶酶体不稳定。此外，用M β CD处理溶酶体引起溶酶体质子泄漏，并提高了溶酶体内pH值。结果表明，膜胆固醇在维持溶酶体对K+和H+的有限渗透性中起着重要作用。这种膜固醇的损失对于细胞器酸化和稳定性至关重要。(c)2008 Elsevier B. V.保留所有权利。
Cholesterol is an essential component of lysosomal membranes. In this study, we investigated the effects of membrane cholesterol on the permeability of rat liver lysosomes to K+ and H+, and the organelle stability. Through the measurements of lysosomal beta-hexosaminidase free activity, membrane potential, membrane fluidity, intra-lysosomal pH, and lysosomal proton leakage, we established that methyl-beta-cyclodextrin (M beta CD)-produced loss of membrane cholesterol could increase the lysosomal permeability to both potassium ions and protons, and fluidize the lysosomal membranes. As a result, potassium ions entered the lysosomes through K+/H+ exchange, which produced osmotic imbalance across the membranes and osmotically destabilized the lysosomes. In addition, treatment of the lysosomes with M beta CD caused leakage of the lysosomal protons and raised the intra-lysosomal pH. The results indicate that membrane cholesterol plays important roles in the maintenance of the lysosomal limited permeability to K+ and H+. Loss of this membrane sterol is critical for the organelle acidification and stability. (c) 2008 Elsevier B.V. All rights reserved.