title: A gene network regulating lysosomal biogenesis and function.
abstract: 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.
authors: Telethon Institute of Genetics and Medicine, Via P. Castellino 111, 80131 Naples, Italy.
authors: Marco
authors: M
authors: Sardiello
authors: Michela
authors: M
authors: Palmieri
authors: Alberto
authors: A
authors: di Ronza
authors: Diego Luis
authors: DL
authors: Medina
authors: Marta
authors: M
authors: Valenza
authors: Vincenzo Alessandro
authors: VA
authors: Gennarino
authors: Chiara
authors: C
authors: Di Malta
authors: Francesca
authors: F
authors: Donaudy
authors: Valerio
authors: V
authors: Embrione
authors: Roman S
authors: RS
authors: Polishchuk
authors: Sandro
authors: S
authors: Banfi
authors: Giancarlo
authors: G
authors: Parenti
authors: Elena
authors: E
authors: Cattaneo
authors: Andrea
authors: A
authors: Ballabio
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D016384:Consensus Sequence; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006801:Humans; D055029:Inverted Repeat Sequences; D008247:Lysosomes / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D011401:Promoter Regions, Genetic; D013395:Sucrose / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064972:TFEB protein, human; D014157:Transcription Factors; D013395:Sucrose