2012
DOI: 10.1038/emboj.2012.32
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A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB

Abstract: A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEBUnder basal conditions TFEB, a master regulator of lysosomal biogenesis, is sequestered in the cytosol due to mTORC1-dependent phosphorylation at the lysosomal membrane. Nutrient starvation or lysosomal dysfunction inhibit mTORC1 activity and induce nuclear translocation of TFEB inducing target gene expression.

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Cited by 1,631 publications
(1,920 citation statements)
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“…Exactly how this happens is still under investigation but appearsto require ATP hydrolysis and an associated rotation of the v-ATPase stalk. Interestingly, mTORC1 also negatively regulates lysosome biogenesis (Settembre et al 2012), indicating that mTORC1 might also play an important role in controlling the number of lysosomes in the cell. Importantly, much of the understanding of the nutrient-sensing mechanism has been solved in vitro, and it will be important in future studies to determine the extent to which the amino acid-sensing pathway functions in various tissues and tumor cells.…”
Section: The Mtor Complexes and Their Regulationmentioning
confidence: 99%
“…Exactly how this happens is still under investigation but appearsto require ATP hydrolysis and an associated rotation of the v-ATPase stalk. Interestingly, mTORC1 also negatively regulates lysosome biogenesis (Settembre et al 2012), indicating that mTORC1 might also play an important role in controlling the number of lysosomes in the cell. Importantly, much of the understanding of the nutrient-sensing mechanism has been solved in vitro, and it will be important in future studies to determine the extent to which the amino acid-sensing pathway functions in various tissues and tumor cells.…”
Section: The Mtor Complexes and Their Regulationmentioning
confidence: 99%
“…27 Moreover, ULK1 is subject to ubiquitination mediated by AMBRA1 (autophagy/beclin-1 regulator 1) under proautophagic conditions, stabilizing this kinase and increasing its activity, whereas AMBRA1 is under the regulation of MTORC1. 61 In addition, MTORC1 negatively regulates lysosomal biogenesis and function via impeding the nuclear translocation of TFEB (transcription factor EB); 23,[62][63][64] therefore, MTORC1 influences the degradative capacity of lysosomes, which provides another link between class I PI3K and autophagy.…”
Section: Regulation Of Autophagy By Class I Pi3ksmentioning
confidence: 99%
“…51 We examined whether fasting, in vivo, is a stimulus for activation of TFEB in the myocardium. Given a lack of consensus on the suitability of the available antibodies in identifying the endogenous TFEB protein, 46,48,52 we first evaluated the specificity of a polyclonal anti-TFEB antibody employed in recent publications to detect endogenous human TFEB; 46 which is predicted to detect murine TFEB based on sequence similarity within the epitope employed in its generation; in a murine atrial myocyte cell line (HL-1 myocytes) and mouse hearts (Fig. S7).…”
Section: Fasting and Refeeding Transcriptionally Modulate The Autophamentioning
confidence: 99%