ArticleAutophagy2024
SMURF1 controls the PPP3/calcineurin complex and TFEB at a regulatory node for lysosomal biogenesis.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 18 citations in OpenAlex.
- De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.Genome research · 2026Article
- Maternal Extracellular Vesicles During Pregnancy and Autism Risk in Children.medRxiv : the preprint server for health sciences · 2026Article
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- OR2T6 modulates autophagy through the PPP3CA-mediated pathways to suppress gastric cancer.Cell death and differentiation · 2026Article
- K48 and K63 linkage-competed ubiquitination of BECN1 promotes circPDE4D-mediated autophagy in chronic obstructive pulmonary disease.Cell death & disease · 2026Article
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- Gal3-CaN-Smurf1 Complex Sequestrates FLCN-FNIPs to Facilitate TFEB Activation in Response to Endomembrane Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A comprehensive analysis of the relationship between inflammasomes and autophagy in human tumors: Recent developments.Journal of cell communication and signaling · 2025Review
- Lysosomal quality control Review.Autophagy · 2025Review
- Buddleoside alleviates nonalcoholic steatohepatitis by targeting the AMPK-TFEB signaling pathway.Autophagy · 2025Article
- Ubiquitin-proteasome system in the different stages of dominantly inherited Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- SMAD specific E3 ubiquitin protein ligase 1 accelerates diabetic macular edema progression by WNT inhibitory factor 1.World journal of diabetes · 2025Article
- Important regulatory role of mitophagy in diabetic microvascular complications.Journal of translational medicine · 2025Review
- SMURF1 mediates damaged lysosomal homeostasis by ubiquitinating PPP3CB to promote the activation of TFEB.Autophagy · 2025Article
- SMURF1-Induced Ubiquitination of FTH1 Disrupts Iron Homeostasis and Suppresses Myogenesis.International journal of molecular sciences · 2025Article
- Exploring the multilayered response of TB bacterium Mycobacterial tuberculosis to lysosomal injury.FEMS microbiology reviews · 2025Review
- Lysosome quality control in health and neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- Ubiquitin-Proteasome System in the Different Stages of Dominantly Inherited Alzheimer's Disease.Research square · 2024Article
- Colonic epithelial cell-specific TFEB activation: a key mechanism promoting anti-bacterial defense in response toFrontiers in microbiology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macroautophagy/autophagy is a homeostatic process in response to multiple signaling, such as the lysosome-dependent recycling process of cellular components. Starvation-induced MTOR inactivation and PPP3/calcineurin activation were shown to promote the nuclear translocation of TFEB. However, the mechanisms via which signals from endomembrane damage are transmitted to activate PPP3/calcineurin and orchestrate autophagic responses remain unknown. This study aimed to show that autophagy regulator SMURF1 controlled TFEB nuclear import for transcriptional activation of the lysosomal biogenesis. We showed that blocking SMURF1 affected lysosomal biogenesis in response to lysosomal damage by preventing TFEB nuclear translocation. It revealed galectins recognized endolysosomal damage, and led to recruitment of SMURF1 and the PPP3/calcineurin apparatus on lysosomes. SMURF1 interacts with both LGALS3 and PPP3CB to form the LGALS3-SMURF1-PPP3/calcineurin complex. Importantly, this complex further stabilizes TFEB, thereby activating TFEB for lysosomal biogenesis. We determined that LLOMe-mediated TFEB nuclear import is dependent on SMURF1 under the condition of MTORC1 inhibition. In addition, SMURF1 is required for PPP3/calcineurin activity as a positive regulator of TFEB. SMURF1 controlled the phosphatase activity of the PPP3CB by promoting the dissociation of its autoinhibitory domain (AID) from its catalytic domain (CD). Overexpression of SMURF1 showed similar effects as the constitutive activation of PPP3CB. Thus, SMURF1, which bridges environmental stress with the core autophagosomal and autolysosomal machinery, interacted with endomembrane sensor LGALS3 and phosphatase PPP3CB to control TFEB activation.
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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 OpenQuestion graph.