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TFEB Links Autophagy to Lysosomal Biogenesis
Open accessAbstract
Starvation activates a transcriptional program controlling autophagosome formation, lysosome fusion, and substrate degradation.
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“Transcription factor E3 (TFE3) and transcription factor EB (TFEB) are two major members of the microphthalmia-transcription factor E (MiT/TFE) subfamily and well characterized as master regulators of lysosome biogenesis and autophagy1–4.”
From PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson’s disease (2024) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A gene regulatory network, named CLEAR (coordinated lysosomal enhancement and regulation) that controls both lysosome and autophagosome biogenesis was identified using a systemsbiology approach.[463][464][465]”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [463]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In a first case, starting from experimental data available in the literature, we identified 20 targets related to autophagy activation and validated them by qPCR: ATG10, ATG14, ATG16L1, ATG3, ATG4, ATG7, ATG9A, BCL2, GABARAP, GABARAPL1, MAP1LC3B, NBR1, OPTN, PINK1, SQSTM1, ULK1, ULK2, UVRAG, WDR45, WIPI1 (Fig. 2) [18–27].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, retromer-knockout cells display activation of the TFEB transcription factors (Curnock et al., 2019), master regulators of cellular nutrient sensing and energy metabolism (Sardiello et al., 2009; Settembre et al., 2011).”
From Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting (2020) · cites this paper as Settembre et al., 2011
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“NRF2 or TFEB pathways were unaltered as shown by the lack of change in the level of NQO-1 and HO-1, two major targets of NRF2, or the intensity of nuclear TFEB in response to hα-Syn46,47 (Supplementary Fig. 4i, j).”
From Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration (2020) · cites this paper as [47]
The cited source says what the claim attributes to it.
In the citing paper
“TFEB activity is regulated by starvation, 463 and can thus serve as a new tool for monitoring transcriptional regulation connected with autophagy.”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [463]
The cited source says what the claim attributes to it.
In the citing paper
“For example, this can be achieved either through overexpression or post-translational activation of the gene encoding TFEB (see Transcriptional and translational regulation), a transcriptional regulator of the biogenesis of both lysosomes and autophagosomes.463,464”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [463]
The cited source says what the claim attributes to it.
In the citing paper
“This transcription factor regulates expression of lysosome biogenesis genes [31].”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [31]
The cited source says what the claim attributes to it.
In the citing paper
“we identified that Tfeb, transcription factor and modulator of lysosome biogenesis [31], may be targeted by miR-155.”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [31]
The cited source says what the claim attributes to it.
In the citing paper
“A so called “activation list” has been derived from the comparison of publications, in which we reported conditions of gene up-regulation upon autophagy activation [18–27].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“Hence, for the second sub-lists, we identified 26 targets to assess the state of lysosomal biogenesis (Fig. 2) at variance with the autophagy activation list, this sub-list has been realized by only comparing data from recent work, in which mRNA levels of lysosomal genes in response to autophagy enhancement were accurately and experimentally examined [15, 18, 19, 28–30].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“The restricted “induction list” for the prediction of autophagy activation state, made by 20 targets, was obtained combining data from previous publications [18–27], in which have been documented the increase of the mRNA expression following autophagy induction.”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“Similarly, the list for the evaluation of “lysosomal biogenesis” was created from literature by combining data that underwent preceding experimental validation [15, 18, 19, 28–30].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [18]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“NRF2 or TFEB pathways were unaltered as shown by the lack of change in the level of NQO-1 and HO-1, two major targets of NRF2, or the intensity of nuclear TFEB in response to hα-Syn46,47 (Supplementary Fig. 4i, j).”
From Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration (2020) · cites this paper as [47]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The “lysosomal biogenesis list” resulted instead from an extensive literature analysis, obtained by combining data that underwent previous experimental validation [15, 18, 19, 28–30].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [18]
Experimental — accuracy not yet measuredIn the citing paper
“Global regulation of the myriad effectors and phases of autophagy is overseen by TFEB (transcription factor EB), a basic helix-loop-helix leucine zipper that directs expression of autophagy and lysosomal genes comprising the coordinated lysosomal expression and regulation (CLEAR) network by binding to a conserved promoter motif [47,48].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [48]
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Self-citation
Metadata
- Authors
- Settembre, C., Di Malta, C., Polito, V. A., Arencibia, M. G., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Medina, D., Colella, P., Sardiello, M., Rubinsztein, D. C., & Ballabio, A.
- Affiliations
- Baylor College of Medicine (US)
- Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.
- Cambridge Institute for Medical Research, Wellcome Trust–Medical Research Council Building, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0XY, UK.
- Telethon Institute Of Genetics And Medicine (IT)
- Addenbrooke's Hospital (GB)
- Corresponding author
- Ballabio, Andrea
- ORCID
- Venue
- Science
- Published
- 2011-06-17
- Volume
- 332
- Issue
- 6036
- Pages
- 1429-1433
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3638014
- OpenAlex
- W1975200363
- Cited by
- 3,365
- References
- 33
- Citations by year
- 2026: 283 · 2025: 275 · 2024: 287 · 2023: 270 · 2022: 328 · 2021: 290 · 2020: 317 · 2019: 251 · 2018: 227 · 2017: 192 · 2016: 184 · 2015: 152 · 2014: 116 · 2013: 96 · 2012: 66
- FWCI
- 73.01
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-12-18)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Acceda (Universidad de Las Palmas de Gran Canaria) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute of Neurological Disorders and Stroke (R01NS078072)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD024064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- TFEB, autophagy, lysosomal biogenesis, starvation, autophagosome-lysosome fusion, autophagosome formation, substrate degradation, serine phosphorylation, ERK2, mitogen-activated protein kinase, nutrient sensing, transcriptional regulation, nuclear localization
- MeSH terms
- Animals, Autophagy, Cell Nucleus, Cells, Cultured, Chlorocebus aethiops, Cytoplasm, Gene Expression Regulation, HeLa Cells, Humans, Liver, Lysosomes, Mice, Transgenic, Microtubule-Associated Proteins, Phagosomes, Phosphorylation, Transcription, Genetic, Up-Regulation, COS Cells, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, Active Transport, Cell Nucleus, RNA Interference, Mice, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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