ArticleThe EMBO journal2024
Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- TBK1 activity regulates the directionality of axonal transport of signalling endosomes.Life science alliance · 2026Article
- TANK-binding kinase 1 protects against MASH progression via mitochondrial quality control.Experimental & molecular medicine · 2026Article
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- Glutamic Acid at Position 168 Is a Constitutive Activator of Tank Binding Kinase 1 Catalytic Function.Neuromolecular medicine · 2025Article
- BLTP3A is associated with membranes of the late endocytic pathway and is an effector of CASM.The EMBO journal · 2025Article
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- Article
- Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.bioRxiv : the preprint server for biology · 2025Article
- The bridge-like lipid transport protein VPS13C/PARK23 mediates ER-lysosome contacts following lysosome damage.Nature cell biology · 2025Article
- A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes.The Journal of cell biology · 2025Article
- The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.Autophagy reports · 2025Review
- Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment.Journal of cell science · 2025Article
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3 authors.
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Abstract
Lysosomes play a pivotal role in coordinating macromolecule degradation and regulating cell growth and metabolism. Despite substantial progress in identifying lysosomal signaling proteins, understanding the pathways that synchronize lysosome functions with changing cellular demands remains incomplete. This study uncovers a role for TANK-binding kinase 1 (TBK1), well known for its role in innate immunity and organelle quality control, in modulating lysosomal responsiveness to nutrients. Specifically, we identify a pool of TBK1 that is recruited to lysosomes in response to elevated amino acid levels. This lysosomal TBK1 phosphorylates Rab7 on serine 72. This is critical for alleviating Rab7-mediated inhibition of amino acid-dependent mTORC1 activation. Furthermore, a TBK1 mutant (E696K) associated with amyotrophic lateral sclerosis and frontotemporal dementia constitutively accumulates at lysosomes, resulting in elevated Rab7 phosphorylation and increased mTORC1 activation. This data establishes the lysosome as a site of amino acid regulated TBK1 signaling that is crucial for efficient mTORC1 activation. This lysosomal pool of TBK1 has broader implications for lysosome homeostasis, and its dysregulation could contribute to the pathogenesis of ALS-FTD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.