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Cited by 135Autophagy in Disease and TherapyCalcium signaling and nucleotide metabolismGlycogen Storage Diseases and Myoclonus

Transcription factor EB: from master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases

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Sardiello, Marco·2016·Annals of the New York Academy of Sciences
DOI 10.1111/nyas.13131PMC PMC5032832
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Abstract

The lysosome is the main catabolic hub of the cell. Owing to its role in fundamental processes such as autophagy, plasma membrane repair, mTOR signaling, and maintenance of cellular homeostasis, the lysosome has a profound influence on cellular metabolism and human health. Indeed, inefficient or impaired lysosomal function has been implicated in the pathogenesis of a number of degenerative diseases affecting various organs and tissues, most notably the brain, liver, and muscle. The discovery of the coordinated lysosomal expression and regulation (CLEAR) genetic program and its master controller, transcription factor EB (TFEB), has provided an unprecedented tool to study and manipulate lysosomal function. Most lysosome‐based processes—including macromolecule degradation, autophagy, lysosomal exocytosis, and proteostasis—are under the transcriptional control of TFEB. Interestingly, impaired TFEB signaling has been suggested to be a contributing factor in the pathogenesis of several degenerative storage diseases. Preclinical studies based on TFEB exogenous expression to reinstate TFEB activity or promote CLEAR network–based lysosomal enhancement have highlighted TFEB as a candidate therapeutic target for the treatment of various degenerative storage diseases.

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  • During fasting or mTOR inhibition, activation of MiT/TFE transcription factors occurs, fostering lysosomal gene expression.

    “during fasting or mTOR inhibition, activation of MiT/TFE transcription factors occurs, with this fostering lysosomal gene expression [47]”

    From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [47]

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Authors
Sardiello, M.
Affiliations
Baylor College of Medicine (US)
Corresponding author
Sardiello, Marco
ORCID
Sardiello, Marco
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2016-05
Volume
1371
Issue
1
Pages
3-14
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1111/nyas.13131
PMC
PMC5032832
OpenAlex
W2436851548
Cited by
135
References
3
Citations by year
2026: 7 · 2025: 8 · 2024: 6 · 2023: 19 · 2022: 8 · 2021: 17 · 2020: 24 · 2019: 15 · 2018: 21 · 2017: 6 · 2016: 4
FWCI
2.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Annals of the New York Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (NS079618)
  • Beyond Batten Disease Foundation
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
Keywords
TFEB, lysosomes, lysosomal storage disease, autophagy, lysosomal exocytosis, proteostasis, lysosomal function
MeSH terms
Animals, Humans, Lysosomes, Models, Biological, Signal Transduction, Lysosomal Storage Diseases, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Molecular Targeted Therapy

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