ArticleNature chemical biology2019
Covalent targeting of the vacuolar H
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
110 citing papers in PubMed, 181 citations in OpenAlex.
- mTORC1 Activation Links Chronic Stress to Meso-Circuit Desynchronization and Accelerated Amyloid Pathology via Autophagic Dysfunction.CNS neuroscience & therapeutics · 2026Article
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- A narrative review on the role of autophagy in male infertility-associated sperm abnormalities.Asian journal of andrology · 2026Review
- Discovery of Autophagy Modulators that Increase I1061T NPC1 Expression and Promote Cholesterol Efflux in Niemann-Pick Type C Patient-Derived Fibroblasts.ACS chemical biology · 2026Article
- ATP13A2 restrains macrophage NLRP3 inflammasome activation to repress neurodegeneration via modulating mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multimodal imaging reveals a lysosomal drug reservoir that drives heterogeneous distribution of PARP inhibitors.Nature communications · 2026Article
- Ginsenoside Rg5 inhibits colorectal cancer, at least partially by blocking the lysosomal degradation of colorectal cancer cells.Scientific reports · 2026Article
- DNA nanodevices detect an acidic nanolayer on the lysosomal surface.Nature cell biology · 2026Article
- Real-time visualization of drug-target interactions in native subcellular microenvironments for lysosome-targeted drug discovery.Journal of pharmaceutical analysis · 2026Article
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- Oxidative Stress and Lysosomal Dysfunction in Neurodegenerative Diseases: Underlying Mechanisms and Nanotherapeutic Targeting Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Lysosomes as chemical and metabolic organizers of central nervous system injury and repair.Frontiers in chemistry · 2026Review
- Lysosome trafficking across intracellular and intercellular networks in the brain.Frontiers in molecular neuroscience · 2026Article
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules.ACS central science · 2025Article
- Failure of lysosomal acidification and endomembrane network in neurodegeneration.Experimental & molecular medicine · 2025Review
- Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol.Nature communications · 2025Article
- Senescence-associated lysosomal dysfunction impairs cystine deprivation-induced lipid peroxidation and ferroptosis.Nature communications · 2025Article
- Recent advances in the clinical spectrum and pathomechanisms associated with X-linked myopathy with excessive autophagy and otherJournal of neuromuscular diseases · 2025Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Autophagy is a lysosomal degradation pathway that eliminates aggregated proteins and damaged organelles to maintain cellular homeostasis. A major route for activating autophagy involves inhibition of the mTORC1 kinase, but current mTORC1-targeting compounds do not allow complete and selective mTORC1 blockade. Here, we have coupled screening of a covalent ligand library with activity-based protein profiling to discover EN6, a small-molecule in vivo activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal v-ATPase, which activates mTORC1 via the Rag guanosine triphosphatases. EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. Consistently, EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner. Our results provide insight into how the v-ATPase regulates mTORC1, and reveal a unique approach for enhancing cellular clearance based on covalent inhibition of lysosomal mTORC1 signaling.
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What OpenQuestion holds
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.