ArticleBiomolecules2020
High Levels of ROS Impair Lysosomal Acidity and Autophagy Flux in Glucose-Deprived Fibroblasts by Activating ATM and Erk Pathways.
Article in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.Redox report : communications in free radical research · 2026Article
- Amelioration of gentamicin-induced acute kidney injury by trifluoperazine: in vivo mechanistic insights.Scientific reports · 2026Article
- Reduced late endosome/lysosome function promotes SLE through chronic PI3K activity and SHP-1/SHIP-1 defects.JCI insight · 2026Article
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.bioRxiv : the preprint server for biology · 2026Article
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- Involvement of endolysosome iron in HIV-1 gp120-, morphine-, and iron supplementation-induced disruption of the reactive species interactome and induction of neurotoxicity.Redox report : communications in free radical research · 2025Article
- SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes.Journal of neuroinflammation · 2025Article
- Simultaneous Live Mapping of pH and Hydrogen Peroxide Fluctuations in Autophagic Vesicles.JACS Au · 2025Article
- Key Mechanisms in Lysosome Stability, Degradation and Repair.Molecular and cellular biology · 2025Review
- Decoding the impact of ageing and environment stressors on skin cell communication.Biogerontology · 2024Review
- 27-Hydroxycholesterol Enhances Secretion of Extracellular Vesicles by ROS-Induced Dysregulation of Lysosomes.Endocrinology · 2024Article
- Phenotypic and Functional Outcomes in Macrophages Exposed to an Environmentally Relevant Mixture of Organophosphate EstersEnvironmental health perspectives · 2024Article
- Cellular Senescence and Extracellular Vesicles in the Pathogenesis and Treatment of Obesity-A Narrative Review.International journal of molecular sciences · 2024Review
- Cholesterol Metabolite 27-Hydroxycholesterol Enhances the Secretion of Cancer Promoting Extracellular Vesicles by a Mitochondrial ROS-Induced Impairment of Lysosomal Function.bioRxiv : the preprint server for biology · 2024Article
- HERV-K (HML-2) Envelope Protein Induces Mitochondrial Depolarization and Neurotoxicity via Endolysosome Iron Dyshomeostasis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- STING dependent BAX-IRF3 signaling results in apoptosis during late-stage Coxiella burnetii infection.Cell death & disease · 2024Article
- C. elegans Presenilin Mediates Inter-Organelle Contacts and Communication that Is Required for Lysosome Activity.Aging and disease · 2024Article
- Cutaneous Redox Senescence.Biomedicines · 2024Review
- Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis.Cell death and differentiation · 2024Article
- Impaired Autophagic Flux in Glucose-Deprived Cells: An Outcome of Lysosomal Acidification Failure Exacerbated by Mitophagy Dysfunction.Molecules and cells · 2023Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Under glucose deprivation, cells heavily mobilize oxidative phosphorylation to maintain energy homeostasis. This leads to the generation of high levels of ATP, as well as reactive oxygen species (ROS), from mitochondria. In nutrient starvation, autophagy is activated, likely to facilitate resource recycling, but recent studies suggest that autophagy flux is inhibited in cells undergoing glucose deprivation. In this study, we analyzed the status of autophagic flux in glucose-deprived human fibroblasts. Although lysosomes increased in quantity due in part to an increase of biogenesis, a large population of them suffered low acidity in the glucose-deprived cells. Autophagosomes also accumulated due to poor autolysis in these cells. A treatment of antioxidants not only restored lysosomal acidity but also released the flux blockade. The inhibition of ataxia telangiectasia mutated (ATM) serine/threonine kinase, which is activated by ROS, also attenuated the impairment of lysosomal acidity and autophagic flux, suggesting an effect of ROS that might be mediated through ATM activation. In addition, the activity of extracellular signal-regulated kinase (Erk) increased upon glucose deprivation, but this was also compromised by a treatment of antioxidants. Furthermore, the Erk inhibitor treatment also alleviated the failure in lysosomal acidity and autophagic flux. These together indicate that, upon glucose deprivation, cells undergo a failure of autophagy flux through an impairment of lysosomal acidity and that a high-level ROS-induced activation of Erk and ATM is involved in this impairment.
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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.