專題：Science報導
來自義大利米蘭大學，Maples大學的一個研究團隊在最新的Science上發表文章，A Gene Network Regulating Lysosomal Biogenesis and Function，發現了一個調節溶酶體功能的基因網絡。
眾所周知，溶酶體（lysosome）為細胞漿內由單層脂蛋白膜包繞的內含一系列酸性水解酶的小體。是細胞內具有單層膜囊狀結構的細胞器，溶酶體內含有許多種水解酶類，能夠分解很多種物質，溶酶體被比喻為細胞內的「酶倉庫」「消化系統」 「細胞垃圾處理站」。
溶酶體可以將有害的分子進行分解，包括那些在阿茲海默症、亨廷頓氏病和帕金森氏病以及許多所謂的「溶酶體貯積症」患者的細胞中所積聚的有害分子。
Marco Sardiello等人發現，溶酶體細胞器的合成以及功能的執行受一個基因網路的調控，這些基因間的協調表達受轉錄因子TFEB控制。TFEB本身可以在溶酶體功能障礙的時候被激活。它可調節細胞中溶酶體的豐富程度以及其降解複雜分子的能力。
Marco Sardiello研究小組以大鼠細胞為模型驗證他們的理論。結果發現，增加TFEB的活性可幫助溶酶體降解引起亨廷頓氏病的蛋白。
這些研究成果可能為阿茲海默症、亨廷頓氏病和帕金森氏病的治療帶來新的思路。（生物谷Bioon.com）
生物谷推薦原始出處：
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.