A gene network regulating lysosomal biogenesis and function.
Science, 2009/7/24;325(5939):473-7.
Sardiello M[1], Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A
Affiliations
PMID: 19556463DOI: 10.1126/science.1174447
Impact factor: 63.714
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.
MeSH terms
Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cells, Cultured; Chromatin Immunoprecipitation; Consensus Sequence; Gene Regulatory Networks; HeLa Cells; Humans; Inverted Repeat Sequences; Lysosomes; Mice; Promoter Regions, Genetic; Sucrose; Transcription Factors
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