A Gene Network Regulating Lysosomal Biogenesis and Function

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 fact...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2009-07, Vol.325 (5939), p.473-477
Main Authors: Sardiello, Marco, Palmieri, Michela, di Ronza, Alberto, Medina, Diego Luis, Valenza, Marta, Gennarino, Vincenzo Alessandro, Di Malta, Chiara, Donaudy, Francesca, Embrione, Valerio, Polishchuk, Roman S., Banfi, Sandro, Parenti, Giancarlo, Cattaneo, Elena, Ballabio, Andrea
Format: Article
Language:English
Subjects:
A gene
Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism
Biological and medical sciences
Cell structures and functions
Cells
Cells, Cultured
Cellular biology
Cellular immunity
Chromatin Immunoprecipitation
Consensus Sequence
Enzymes
Fundamental and applied biological sciences. Psychology
Gene expression
Gene expression regulation
Gene Regulatory Networks
Genes
HeLa Cells
Humans
Inverted Repeat Sequences
Lysosome, phagosome
Lysosomes
Lysosomes - genetics
Lysosomes - physiology
Messenger RNA
Mice
Microscopy
Molecular and cellular biology
Molecular biology
Molecules
Neurodegenerative diseases
Promoter Regions, Genetic
Sucrose - metabolism
Transcription Factors - metabolism
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1174447