ArticleDisease models & mechanisms2023
Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells.
Article in Disease models & mechanisms, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Lipid-driven membrane remodeling engages a lysosome-dependent adaptive repair program during retinal aging.Molecular neurodegeneration · 2026Article
- VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair.Nature communications · 2026Article
- Single-cell RNA sequencing reveals lipid metabolism disorders in the retina in spontaneous high myopia.Biology direct · 2026Article
- The Molecular Basis of Ocular Aging: Mechanisms, Pathologies, and Emerging Therapeutics.Investigative ophthalmology & visual science · 2026Review
- Exosomal Profiling Reveals Mechanisms of Hibernation-Associated Neuroprotection.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of SLC11A1-Mediated Lysosomal Iron Accumulation in Microglia Promotes Repair Following White Matter Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PRKCQ-TRIM22 axis promotes proliferation and metastasis of oral squamous cell carcinoma via autophagosome‒lysosome pathway activation.Cancer cell international · 2026Article
- Association of Clinical Severity in Autism Spectrum Disorder with Biomolecules Involved in Lipid Metabolism, Inflammation and miRNAs.Biomolecules · 2026Article
- PLGA nanoparticles restore acidic pH and degradative function to compromised lysosomes with Cy3-labeling providing enhanced tracking to lysosomes.American journal of physiology. Cell physiology · 2026Article
- Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.Research square · 2026Article
- NLRP3 Inflammasome Activation in Oxidative Stress: A Key Mechanism Driving Neuroinflammation.Neuroimmunomodulation · 2026Review
- NCOA4 as a regulatory switch linking DNA damage to lipid peroxidation in radiation response.Frontiers in cell and developmental biology · 2026Review
- Review
- Oral Ursodeoxycholic Acid Is Associated With Decreased Rate of AMD.Clinical therapeutics · 2025Article
- LAPTM4B as a key regulator in the copper-induced endoplasmic reticulum-lysosome interplay disorder in duck liver and the protective role of baicalin.Journal of animal science and biotechnology · 2025Article
- Sustained Lysosomal Delivery of Enhanced Cy3-Labeled Acid Nanoparticles Restores Lysosomal pH in Retinal Pigment Epithelial Cells and Astrocytes.bioRxiv : the preprint server for biology · 2025Article
- Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2025Review
- Reassessing the role of nitric oxide in the pathogenesis of sphincter of Oddi dysfunction.Gastroenterology report · 2025Review
- Lysosomes' fallback strategies: more than just survival or death.Frontiers in cell and developmental biology · 2025Review
- The Molecular Determinants of Erythrocyte Removal Impact the Development of Metabolic Dysfunction-Associated Steatohepatitis.Endocrine, metabolic & immune disorders drug targets · 2025Review
Corrections and comments
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Authors and funding
26 authors at 5 institutions in 1 country.
Funding
Abstract
Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, the leading cause of blindness in older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured induced pluripotent stem cell-derived RPE cells increased lysosomal abundance, impaired proteolysis and reduced the activity of a subset of lysosomal enzymes, including lysosomal acid lipase (LIPA) and acid sphingomyelinase (SMPD1). In a liver-specific Hepc (Hamp) knockout murine model of systemic iron overload, RPE cells accumulated lipid peroxidation adducts and lysosomes, developed progressive hypertrophy and underwent cell death. Proteomic and lipidomic analyses revealed accumulation of lysosomal proteins, ceramide biosynthetic enzymes and ceramides. The proteolytic enzyme cathepsin D (CTSD) had impaired maturation. A large proportion of lysosomes were galectin-3 (Lgals3) positive, suggesting cytotoxic lysosomal membrane permeabilization. Collectively, these results demonstrate that iron overload induces lysosomal accumulation and impairs lysosomal function, likely due to iron-induced lipid peroxides that can inhibit lysosomal enzymes.
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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 Socratic graph.