ArticleMolecular cell2020
AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 184 citations in OpenAlex.
- Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons.iScience · 2026Article
- Glycoprotein-induced phase separation drives unconventional secretion of galectin-3.Nature communications · 2026Article
- Selective autophagy in kidney health and disease.Nature reviews. Nephrology · 2026Review
- Review
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- AMPK-NLRP3 Inflammasome Crosstalk: Structural Insights, Molecular Mechanisms, and Therapeutic Implications for Inflammation and Neuroinflammation.Molecular neurobiology · 2026Review
- Glycobiology-driven therapeutic targeting of glycan-binding proteins: mechanisms, diseases, and clinical translation.Signal transduction and targeted therapy · 2026Review
- Galectin-9 activates microglial asparagine endopeptidase and promotes α-synuclein pathology in Parkinson's disease.Cell death and differentiation · 2026Article
- Lysosomal magneto-mechanics rewire immunity.Cell research · 2026Article
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- AMPK is dispensable for physiological podocyte and glomerular functions but prevents glomerular fibrosis in experimental diabetes.Cell death discovery · 2026Article
- Mechanistic Modulation of Autophagy by Bioactive Natural Products: Implications for Human Aging and Longevity.Nutrients · 2026Review
- Dynamic magneto-mechanical force in lysosomes induces durable macrophage repolarization for antitumor immunity.Cell research · 2026Article
- Membrane atg8ylation and autophagy in protection against Mycobacterium tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Timosaponin A-III Induces ROS-mediated Apoptosis and Triggers Protective AutophagyAnti-cancer agents in medicinal chemistry · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Enduring Effects of Humanin on Mitochondrial Systems in TBI Pathology.Biomolecules · 2025Article
- ATG16L1 controls mammalian vacuolar proton ATPase.The Journal of cell biology · 2025Article
- Article
- Processing bodies promote lysosomal quality control and cell survival during recovery from lysosomal damage.Research square · 2025Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
AMPK is a central regulator of metabolism and autophagy. Here we show how lysosomal damage activates AMPK. This occurs via a hitherto unrecognized signal transduction system whereby cytoplasmic sentinel lectins detect membrane damage leading to ubiquitination responses. Absence of Galectin 9 (Gal9) or loss of its capacity to recognize lumenal glycans exposed during lysosomal membrane damage abrogate such ubiquitination responses. Proteomic analyses with APEX2-Gal9 have revealed global changes within the Gal9 interactome during lysosomal damage. Gal9 association with lysosomal glycoproteins increases whereas interactions with a newly identified Gal9 partner, deubiquitinase USP9X, diminishes upon lysosomal injury. In response to damage, Gal9 displaces USP9X from complexes with TAK1 and promotes K63 ubiquitination of TAK1 thus activating AMPK on damaged lysosomes. This triggers autophagy and contributes to autophagic control of membrane-damaging microbe Mycobacterium tuberculosis. Thus, galectin and ubiquitin systems converge to activate AMPK and autophagy during endomembrane homeostasis.
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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.