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Cell:溶酶体过氧化物酶体助力胆固醇转运

2015-04-13 佚名 生物谷

近日,武汉大学宋保亮研究组在著名国际期刊cell发表了他们的一项最新研究进展,他们发现胆固醇在细胞内的转运需要溶酶体与过氧化物酶体的膜相互作用,揭示了过氧化物酶体在胆固醇细胞内转运中的重要作用。 胆固醇是真核细胞内一种重要脂类物质,对于内质网脂蛋白的储存和分泌具有非常重要的作用。同时,胆固醇在细胞内的异常积累会引起严重疾病,如遗传性神经变性疾病C型尼曼匹克病。因此,研究胆固醇在细胞内的动

近日,武汉大学宋保亮研究组在著名国际期刊cell发表了他们的一项最新研究进展,他们发现胆固醇在细胞内的转运需要溶酶体与过氧化物酶体的膜相互作用,揭示了过氧化物酶体在胆固醇细胞内转运中的重要作用。
 
胆固醇是真核细胞内一种重要脂类物质,对于内质网脂蛋白的储存和分泌具有非常重要的作用。同时,胆固醇在细胞内的异常积累会引起严重疾病,如遗传性神经变性疾病C型尼曼匹克病。因此,研究胆固醇在细胞内的动态转运过程具有重要意义。
 
胆固醇能够在多个细胞器之间发生动态转运,对于多种细胞功能具有非常重要的作用。但是细胞内胆固醇动态转运的机制一直不是特别清楚。研究人员建立了一种基于两性霉素B的实验方法,进行全基因组范围的shRNA筛选,寻找影响低密度脂蛋白胆固醇运输的基因,结果筛选到一些富集的过氧化物酶特定基因特定富集,发现了一条之前从未发现的胆固醇转运途径。
 
研究人员发现过氧化物酶体和溶酶体膜之间存在动态接触,溶酶体膜上的突触小泡蛋白VII能够与过氧化物酶体膜表面的脂质PI(4,5)P2发生结合。LDL-胆固醇会增强溶酶体与过氧化物酶体之间的这种动态接触,将胆固醇从溶酶体转运到过氧化物酶体上。干扰过氧化物酶体关键基因会导致胆固醇在溶酶体中发生积累。
 
总的来说,这项研究揭示了过氧化物酶体在细胞内胆固醇转运中发挥了意想不到的作用,由于胆固醇会在尼曼匹克病病人细胞中和过氧化物酶体紊乱的小鼠模型中大量积累,因此该转运途径的发现对于相关疾病研究具有重要意义。

原始出处:

Bei-Bei Chu5, Ya-Cheng Liao5, Wei Qi, Chang Xie, Ximing Du, Jiang Wang, Hongyuan Yang, Hong-Hua Miao, Bo-Liang Li, Bao-Liang Song. Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts. Cell, April 9, 2015, 161(2):291-306. doi:10.1016/j.cell.2015.02.019

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    2016-03-01 维他命
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    2015-09-12 yzh409
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