来自意大利米兰大学，Maples大学的一个研究团队在最新的Science上发表文章，A Gene Network Regulating Lysosomal Biogenesis and Function，发现了一个调节溶酶体功能的基因网络。
众所周知，溶酶体（lysosome）为细胞浆内由单层脂蛋白膜包绕的内含一系列酸性水解酶的小体。是细胞内具有单层膜囊状结构的细胞器，溶酶体内含有许多种水解酶类，能够分解很多种物质，溶酶体被比喻为细胞内的“酶仓库”“消化系统” “细胞垃圾处理站”。
溶酶体可以将有害的分子进行分解，包括那些在阿兹海默症、亨廷顿氏病和帕金森氏病以及许多所谓的“溶酶体贮积症”患者的细胞中所积聚的有害分子。
Marco Sardiello等人发现，溶酶体细胞器的合成以及功能的执行受一个基因网路的调控，这些基因间的协调表达受转录因子TFEB控制。TFEB本身可以在溶酶体功能障碍的时候被激活。它可调节细胞中溶酶体的丰富程度以及其降解复杂分子的能力。
Marco Sardiello研究小组以大鼠细胞为模型验证他们的理论。结果发现，增加TFEB的活性可帮助溶酶体降解引起亨廷顿氏病的蛋白。
这些研究成果可能为阿兹海默症、亨廷顿氏病和帕金森氏病的治疗带来新的思路。（生物谷Bioon.com）
生物谷推荐原始出处：
Science June 25, 2009 DOI: 10.1126/science.1174447
A Gene Network Regulating Lysosomal Biogenesis and Function
Marco Sardiello 1, Michela Palmieri 1, Alberto di Ronza 1, Diego Luis Medina 1, Marta Valenza 2, Vincenzo Alessandro Gennarino 1, Chiara Di Malta 1, Francesca Donaudy 1, Valerio Embrione 1, Roman S. Polishchuk 3, Sandro Banfi 1, Giancarlo Parenti 4, Elena Cattaneo 2, Andrea Ballabio 4*
1 Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy.
2 Department of Pharmacological Sciences and Center for Stem Cell Research, University. of Milan, Via Balzaretti 9, 20133 Milan, Italy.
3 Telethon Electron Microscopy Core Facility, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, I-66030 Santa Maria Imbaro, Chieti, Italy.
4 Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy.; Department of Pediatrics, Federico II University, Via S. Pansini 5, 80131 Naples, Italy.
Lysosomes are organelles central to degradation and recycling processes in animal cells. Whether lysosomal activity is coordinated to respond to cellular needs remains unclear. We found that most lysosomal genes exhibit coordinated transcriptional behavior and are regulated by the transcription factor TFEB. Under aberrant lysosomal storage conditions, TFEB translocated from the cytoplasm to the nucleus, resulting in the activation of its target genes. TFEB overexpression in cultured cells induced lysosomal biogenesis and increased the degradation of complex molecules, such as glycosaminoglycans (GAGs) and the pathogenic protein causing Huntington disease. Thus, a genetic program controls lysosomal biogenesis and function, providing a potential therapeutic target to enhance cellular clearing in lysosomal storage disorders and neurodegenerative diseases.
