Article

A Gene Network Regulating Lysosomal Biogenesis and Function

Telethon Institute of Genetics and Medicine, Via P. Castellino 111, 80131 Naples, Italy.
Science (Impact Factor: 31.48). 07/2009; 325(5939):473-7. DOI: 10.1126/science.1174447
Source: PubMed

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.

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Available from: Michela Palmieri, Aug 22, 2015
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