ArticlePloS one2017
Lysosomal adaptation: How cells respond to lysosomotropic compounds.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.Nature communications · 2020Pooled it
- Stage-adaptive integration of polydopamine promotes human pluripotent stem cell-derived alveolar organoids differentiation and maturation.Materials today. Bio · 2026Article
- Reduced late endosome/lysosome function promotes SLE through chronic PI3K activity and SHP-1/SHIP-1 defects.JCI insight · 2026Article
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- Pimozide enhances antigen cross-presentation and promotes cytotoxic CD8+ T cell immunity by stimulating dendritic cells.Frontiers in immunology · 2026Article
- Antitumoral Efficacy of AuNRs-Laden ECFCs In Vitro and In Vivo: Decoding the Heat and Rays Combo Treatment in Breast Cancer and Melanoma Cells.Advanced healthcare materials · 2025Article
- Early endolysosomal dysfunction is a contributing factor to gadolinium-based contrast agent mouse renal proximal tubule epithelial cell injury.Cell biology and toxicology · 2025Article
- Cellular Uptake and Trafficking of Lipid Nanocarriers Using High-Resolution Electron Microscopy.AAPS PharmSciTech · 2025Article
- Environmental Diagnosis through a Flow Cytometric Approach.International journal of molecular sciences · 2024Review
- Reversible Dilated Cardiomyopathy in a Male Patient With Rheumatoid Arthritis: A Case Report.Cureus · 2024Article
- Identification of lysosomotropism using explainable machine learning and morphological profiling cell painting data.RSC medicinal chemistry · 2024Article
- Downregulation of Protease Cathepsin D and Upregulation of Pathologic α-Synuclein Mediate Paucity of DNAJC6-Induced Degeneration of Dopaminergic Neurons.International journal of molecular sciences · 2024Article
- Weak base drug-induced endolysosome iron dyshomeostasis controls the generation of reactive oxygen species, mitochondrial depolarization, and cytotoxicity.NeuroImmune pharmacology and therapeutics · 2024Article
- To eat or not to eat: a critical review on the role of autophagy in prostate carcinogenesis and prostate cancer therapeutics.Frontiers in pharmacology · 2024Review
- Antidepressants enter cells, organelles, and membranes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Altered lipid homeostasis and autophagy precipitate diffuse alveolar hemorrhage in murine lupus.Autophagy reports · 2024Article
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- Impaired Lysosome Reformation in Chloroquine-Treated Retinal Pigment Epithelial Cells.Investigative ophthalmology & visual science · 2023Article
- ARL-17477 is a dual inhibitor of NOS1 and the autophagic-lysosomal system that prevents tumor growth in vitro and in vivo.Scientific reports · 2023Article
28 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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomes are acidic organelles essential for degradation and cellular homoeostasis and recently lysosomes have been shown as signaling hub to respond to the intra and extracellular changes (e.g. amino acid availability). Compounds including pharmaceutical drugs that are basic and lipophilic will become sequestered inside lysosomes (lysosomotropic). How cells respond to the lysosomal stress associated with lysosomotropism is not well characterized. Our goal is to assess the lysosomal changes and identify the signaling pathways that involve in the lysosomal changes. Eight chemically diverse lysosomotropic drugs from different therapeutic areas were subjected to the evaluation using the human adult retinal pigmented epithelium cell line, ARPE-19. All lysosomotropic drugs tested triggered lysosomal activation demonstrated by increased lysosotracker red (LTR) and lysosensor green staining, increased cathepsin activity, and increased LAMP2 staining. However, tested lysosomotropic drugs also prompted lysosomal dysfunction exemplified by intracellular and extracellular substrate accumulation including phospholipid, SQSTM1/p62, GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) and opsin. Lysosomal activation observed was likely attributed to lysosomal dysfunction, leading to compensatory responses including nuclear translocation of transcriptional factors TFEB, TFE3 and MITF. The adaptive changes are protective to the cells under lysosomal stress. Mechanistic studies implicate calcium and mTORC1 modulation involvement in the adaptive changes. These results indicate that lysosomotropic compounds could evoke a compensatory lysosomal biogenic response but with the ultimate consequence of lysosomal functional impairment. This work also highlights a pathway of response to lysosomal stress and evidences the role of TFEB, TFE3 and MITF in the stress response.
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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.