Research ArticleCell Biology

The Nutrient-Responsive Transcription Factor TFE3 Promotes Autophagy, Lysosomal Biogenesis, and Clearance of Cellular Debris

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Science Signaling  21 Jan 2014:
Vol. 7, Issue 309, pp. ra9
DOI: 10.1126/scisignal.2004754

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Regulating Lysosomes and Autophagy

When deprived of nutrients, cells inhibit anabolic processes, such as protein production, and promote catabolic processes, such as those mediated by lysosomes and autophagosomes. Disruption in lysosomal function causes lysosomal storage disorders. Martina et al. discovered that TFE3, like TFEB, another member of the MiTF/TFE (microphthalmia-associated transcription factor and transcription factor E) family, was inhibited at the lysosome under nutrient-replete conditions and translocated to the nucleus to stimulate genes involved in lysosome biogenesis and function and autophagy in response to nutrient deprivation. Data from various tissues and cell lines indicated that TFE3 and TFEB may be cell-specific mediators of lysosomal homeostasis. Overexpression of TFE3 stimulated lysosomal exocytosis and release of debris in a cellular model of a lysosomal storage disorder, thereby providing a potential therapeutic target.

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