TARDBP/TDP-43 regulates autophagy in both MTORC1-dependent and MTORC1-independent manners
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In a recent paper we addressed the mechanism by which defective autophagy contributes to TARDBP/TDP-43-mediated neurodegenerative disorders. We demonstrated that TARDBP regulates MTORC1-TFEB signaling by targeting RPTOR/raptor, a key component and an adaptor protein of MTORC1. Loss of TARDBP decreased the mRNA stability of RPTOR and this regulation in turn enhanced autophagosomal and lysosomal biogenesis in an MTORC1-dependent manner. Meanwhile, loss of TARDBP could also impair autophagosome-lysosome fusion in an MTORC1-independent manner. Importantly, we found that modulation of MTOR activity by treatment with rapamycin and phosphatidic acid had strong effects on the neurodegenerative phenotypes of TBPH (Drosophila TARDBP)-depleted flies. Taken together, our data reveal that multiple dysfunctions in the autophagic process contribute to TARDBP-linked neurodegeneration and may help to identify potential therapeutic targets in the future.
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TARDBP is itself involved in the regulation of autophagy.
“which is itself involved in the regulation of autophagy [276].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [276]
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Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
- Authors
- Ying, Z., Xia, Q., Hao, Z., Xu, D., Wang, M., Wang, H., & Wang, G.
- Affiliations
- Soochow University (CN)
- Corresponding author
- Wang, Hongfeng
- Wang, Guanghui
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-04-02
- Volume
- 12
- Issue
- 4
- Pages
- 707-708
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4836031
- OpenAlex
- W2316895002
- Cited by
- 33
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 2 · 2017: 9 · 2016: 1
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- TARDBP, TDP-43, mTORC1, RPTOR, raptors, mRNA stability, autophagosome-lysosome fusion, lysosomal biogenesis, neurodegeneration, Drosophila, rapamycin, phosphatidic acid, therapeutic target
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Autophagy, DNA-Binding Proteins, Humans, Lysosomes, Phagosomes, Signal Transduction, Multiprotein Complexes, TOR Serine-Threonine Kinases
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