Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 12 June 2012
Vol. 5, Issue 228, p. ra42
[DOI: 10.1126/scisignal.2002790]


Editor's Summary

Sensing Lysosomal Status
Lysosomes clear cells of damaged organelles, cellular debris, and internalized materials. Lysosomal biogenesis requires the transcription factor TFEB, and Roczniak-Ferguson et al. investigated the mechanisms by which lysosomal status controlled the activity of TFEB. They found that TFEB interacted with mTOR (mechanistic target of rapamycin), a kinase that localizes to lysosomes. The mTOR-dependent phosphorylation of TFEB caused TFEB to interact with 14-3-3 proteins, which led to the retention of the transcription factor in the cytoplasm. When lysosomal function was inhibited, TFEB no longer interacted with mTOR, was dephosphorylated, and translocated to the nucleus. Thus, the localization (and thus activity) of TFEB is determined by mTOR-mediated phosphorylation, which in turn reflects lysosomal status.

Citation: A. Roczniak-Ferguson, C. S. Petit, F. Froehlich, S. Qian, J. Ky, B. Angarola, T. C. Walther, S. M. Ferguson, The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis. Sci. Signal. 5, ra42 (2012).

Read the Full Text

Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function.
J. Shin, S. Wang, W. Deng, J. Wu, J. Gao, and X.-P. Zhong (2014)
PNAS 111, E776-E783
   Abstract »    Full Text »    PDF »
GCN5-like Protein 1 (GCN5L1) Controls Mitochondrial Content through Coordinated Regulation of Mitochondrial Biogenesis and Mitophagy.
I. Scott, B. R. Webster, C. K. Chan, J. U. Okonkwo, K. Han, and M. N. Sack (2014)
J. Biol. Chem. 289, 2864-2872
   Abstract »    Full Text »    PDF »
The Nutrient-Responsive Transcription Factor TFE3 Promotes Autophagy, Lysosomal Biogenesis, and Clearance of Cellular Debris.
J. A. Martina, H. I. Diab, L. Lishu, L. Jeong-A, S. Patange, N. Raben, and R. Puertollano (2014)
Science Signaling 7, ra9
   Abstract »    Full Text »    PDF »
The Innate Immune Factor Apolipoprotein L1 Restricts HIV-1 Infection.
H. E. Taylor, A. K. Khatua, and W. Popik (2014)
J. Virol. 88, 592-603
   Abstract »    Full Text »    PDF »
Suppression of Lysosome Function Induces Autophagy via a Feedback Down-regulation of MTOR Complex 1 (MTORC1) Activity.
M. Li, B. Khambu, H. Zhang, J.-H. Kang, X. Chen, D. Chen, L. Vollmer, P.-Q. Liu, A. Vogt, and X.-M. Yin (2013)
J. Biol. Chem. 288, 35769-35780
   Abstract »    Full Text »    PDF »
Histone Methylation Keeps the Brakes on Autophagy.
P. L. Collins and E. M. Oltz (2013)
Mol. Cell. Biol. 33, 3974-3975
   Full Text »    PDF »
Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases.
C. S. Petit, A. Roczniak-Ferguson, and S. M. Ferguson (2013)
J. Cell Biol. 202, 1107-1122
   Abstract »    Full Text »    PDF »
Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease.
C. Spampanato, E. Feeney, L. Li, M. Cardone, J.-A. Lim, F. Annunziata, H. Zare, R. Polishchuk, R. Puertollano, G. Parenti, et al. (2013)
EMBO Mol Med. 5, 691-706
   Abstract »    Full Text »    PDF »
TFEB-mediated autophagy rescues midbrain dopamine neurons from {alpha}-synuclein toxicity.
M. Decressac, B. Mattsson, P. Weikop, M. Lundblad, J. Jakobsson, and A. Bjorklund (2013)
PNAS 110, E1817-E1826
   Abstract »    Full Text »    PDF »
Regulation of mTORC1 and its impact on gene expression at a glance.
M. Laplante and D. M. Sabatini (2013)
J. Cell Sci. 126, 1713-1719
   Full Text »    PDF »
A RANKL-PKC{beta}-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts.
M. Ferron, C. Settembre, J. Shimazu, J. Lacombe, S. Kato, D. J. Rawlings, A. Ballabio, and G. Karsenty (2013)
Genes & Dev. 27, 955-969
   Abstract »    Full Text »    PDF »
Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to lysosomes.
J. A. Martina and R. Puertollano (2013)
J. Cell Biol. 200, 475-491
   Abstract »    Full Text »    PDF »
Processing and Subcellular Trafficking of ER-Tethered EIN2 Control Response to Ethylene Gas.
H. Qiao, Z. Shen, S.-s. C. Huang, R. J. Schmitz, M. A. Urich, S. P. Briggs, and J. R. Ecker (2012)
Science 338, 390-393
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 12 June 2012.
S. M. Ferguson and A. M. VanHook (2012)
Science Signaling 5, pc12
   Abstract »    Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882