A Gene Network Regulating Lysosomal Biogenesis and Function

被引：2075

作者：

Sardiello, Marco ^{[1
]}

Palmieri, Michela ^{[1
]}

di Ronza, Alberto ^{[1
]}

Medina, Diego Luis ^{[1
]}

Valenza, Marta ^{[2
,3
]}

Gennarino, Vincenzo Alessandro ^{[1
]}

Di Malta, Chiara ^{[1
]}

Donaudy, Francesca ^{[1
]}

Embrione, Valerio ^{[1
]}

Polishchuk, Roman S. ^{[4
]}

Banfi, Sandro ^{[1
]}

Parenti, Giancarlo ^{[1
,5
]}

Cattaneo, Elena ^{[2
,3
]}

Ballabio, Andrea ^{[1
,5
]}

机构：

[1] Telethon Inst Genet & Med, I-80131 Naples, Italy

[2] Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy

[3] Univ Milan, Ctr Stem Cell Res, I-20133 Milan, Italy

[4] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Telethon Electron Microscopy Core Facil, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Chieti, Italy

[5] Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy

来源：

SCIENCE | 2009年 / 325卷 / 5939期

关键词：

CATHEPSIN-D; TRANSCRIPTION; EXPRESSION; BRAIN; MODEL; AMINO; BETA;

D O I：

10.1126/science.1174447

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 EB (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 and the pathogenic protein that causes Huntington's 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.

引用

页码：473 / 477

页数：5

共 28 条

[1]

Lysosomal disorders: From storage to cellular damage [J].