ArticleeLife2019
Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
What it found
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The trial behind it
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Who cites it
128 citing papers in PubMed.
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.Redox report : communications in free radical research · 2026Article
- TFEB Attenuates Silver Nanoparticle-Induced Pulmonary Ferroptosis by Preserving Lysosomal Integrity and Limiting Iron Dysregulation.Journal of applied toxicology : JAT · 2026Article
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- TLDc proteins: Stress-responsive nexus regulators of redox signaling, V-ATPase dynamics, and organellar crosstalk in neurodegeneration.Redox biology · 2026Review
- Selenium Nanoparticles Alleviate Intestinal Epithelial Barrier Dysfunction by Coordinating Mitochondria-lysosome Communication under Dual Organelle Stress.Biological trace element research · 2026Article
- Established and emerging roles of lysosomal dysfunction in cardiac aging.Nature cardiovascular research · 2026Review
- Vacuole pH loss triggers ESCRT-dependent plasma membrane remodeling to prevent amino acid toxicity.bioRxiv : the preprint server for biology · 2026Article
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.bioRxiv : the preprint server for biology · 2026Article
- VAMP7-dependent late endosomal secretion of ER and mitochondrial proteins impacts the tumor microenvironment and macrophage engagement.Nature communications · 2026Article
- Cucurbitacin B Inhibits Hepatocellular Carcinoma by Inducing Ferroptosis and Activating the cGAS-STING Pathway.Current issues in molecular biology · 2026Article
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Fe-S Protein FDX1 Triggers Tumor-Intrinsic Innate Immunity via Mitochondrial Nucleic Acids Release to Orchestrate Ferroptosis in CCRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Vacuolar-type HNature communications · 2025Article
- Nanomedicines Against Mitochondrial Dysfunction-Induced Metabolic Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes.Journal of neuroinflammation · 2025Article
- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Parkinson's disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes.bioRxiv : the preprint server for biology · 2025Article
- PI5P4Kα promotes glucose and iron acquisition to support metabolic fitness in pancreatic cancer.Cell reports · 2025Article
- Toxicity of Magnetic Nanoparticles in Medicine: Contributing Factors and Modern Assessment Methods.International journal of molecular sciences · 2025Review
- BDH2-driven lysosome-to-mitochondria iron transfer shapes ferroptosis vulnerability of the melanoma cell states.Nature metabolism · 2025Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Lysosomal acidification is a key feature of healthy cells. Inability to maintain lysosomal acidic pH is associated with aging and neurodegenerative diseases. However, the mechanisms elicited by impaired lysosomal acidification remain poorly understood. We show here that inhibition of lysosomal acidification triggers cellular iron deficiency, which results in impaired mitochondrial function and non-apoptotic cell death. These effects are recovered by supplying iron via a lysosome-independent pathway. Notably, iron deficiency is sufficient to trigger inflammatory signaling in cultured primary neurons. Using a mouse model of impaired lysosomal acidification, we observed a robust iron deficiency response in the brain, verified by in vivo magnetic resonance imaging. Furthermore, the brains of these mice present a pervasive inflammatory signature associated with instability of mitochondrial DNA (mtDNA), both corrected by supplementation of the mice diet with iron. Our results highlight a novel mechanism linking impaired lysosomal acidification, mitochondrial malfunction and inflammation in vivo.
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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.