ArticleAutophagy2021
Trehalose causes low-grade lysosomal stress to activate TFEB and the autophagy-lysosome biogenesis response.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 125 citations in OpenAlex.
- Autophagy and selective autophagy receptors: Key players against Alzheimer's disease.Neural regeneration research · 2026Article
- 1,2-Dichloroethane Induces Neuronal Apoptosis Through AMPK-mTOR-ULK1 Pathway Activation and Autophagic Flux Impairment.Biology · 2026Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Down-Regulation of TFEB With Defective Autophagy in the Susceptibility of Aging Kidneys to Septic Acute Kidney Injury.Aging cell · 2026Article
- Fangchinoline restores TFEB-driven lysosomal biogenesis and blocks H1N1 infection.Acta pharmacologica Sinica · 2026Article
- Nanoplastics Impair Neuroimmune Integrity Via Cellular Retention and Multiple Organelle Stress.Journal of hazardous materials advances · 2026Article
- Lysosome-centered nanomedicine for cancer therapy: mechanisms, materials, and modalities.Journal of nanobiotechnology · 2026Review
- An alkaline nanosized platelet vesicle-based hydrogel for the treatment of osteoporotic bone defects.Materials today. Bio · 2026Article
- ATG5-FOXA3 Axis Contributes to Lysosomal Biogenesis and Auditory Function in Kölliker's Organ.Biomedicines · 2026Article
- Article
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- Mitophagy-NLRP3 Inflammasome Crosstalk in Parkinson's Disease: Pathogenic Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Fragile mitophagy in long COVID: a proposed recovery-failure endotype for post-exertional malaise.Frontiers in medicine · 2026Article
- Lysosomes as chemical and metabolic organizers of central nervous system injury and repair.Frontiers in chemistry · 2026Review
- Biomaterials Promote the Regression of Atherosclerotic Plaque by Regulating Cell Behavior.International journal of nanomedicine · 2026Review
- Telomeric autophagy in human health, aging, and diseases.Frontiers in molecular biosciences · 2026Review
- The Role of TFEB-Regulated Autophagy in Intervertebral Disc Degeneration and Its Therapeutic Potential.Journal of inflammation research · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Apoptotic extracellular vesicles from peripancreatic adipose-derived mesenchymal stem cells ameliorate severe acute pancreatitis through the transcription factor EB-mediated autophagy-lysosomal pathway: an experimental study.International journal of surgery (London, England) · 2025Article
- Human umbilical cord-derived mesenchymal stem cells ameliorate non-alcoholic fatty liver disease via activating TFEB-mediated autophagy in male mice.Stem cell research & therapy · 2025Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
The autophagy-lysosome system is an important cellular degradation pathway that recycles dysfunctional organelles and cytotoxic protein aggregates. A decline in this system is pathogenic in many human diseases including neurodegenerative disorders, fatty liver disease, and atherosclerosis. Thus there is intense interest in discovering therapeutics aimed at stimulating the autophagy-lysosome system. Trehalose is a natural disaccharide composed of two glucose molecules linked by a ɑ-1,1-glycosidic bond with the unique ability to induce cellular macroautophagy/autophagy and with reported efficacy on mitigating several diseases where autophagy is dysfunctional. Interestingly, the mechanism by which trehalose induces autophagy is unknown. One suggested mechanism is its ability to activate TFEB (transcription factor EB), the master transcriptional regulator of autophagy-lysosomal biogenesis. Here we describe a potential mechanism involving direct trehalose action on the lysosome. We find trehalose is endocytically taken up by cells and accumulates within the endolysosomal system. This leads to a low-grade lysosomal stress with mild elevation of lysosomal pH, which acts as a potent stimulus for TFEB activation and nuclear translocation. This process appears to involve inactivation of MTORC1, a known negative regulator of TFEB which is sensitive to perturbations in lysosomal pH. Taken together, our data show the trehalose can act as a weak inhibitor of the lysosome which serves as a trigger for TFEB activation. Our work not only sheds light on trehalose action but suggests that mild alternation of lysosomal pH can be a novel method of inducing the autophagy-lysosome system.
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Registered trials
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.