ArticleCell death & disease2022
Iron-induced cytotoxicity mediated by endolysosomal TRPML1 channels is reverted by TFEB.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- 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
- Dose-Dependent Reprogramming of Chromatin Accessibility by SOX4 Drives the Transcriptional Response to Iron Overload.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death.Journal of cell science · 2026Article
- HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.bioRxiv : the preprint server for biology · 2026Article
- NCOA4 as a regulatory switch linking DNA damage to lipid peroxidation in radiation response.Frontiers in cell and developmental biology · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Fluoride Induces Neurocytotoxicity by Disrupting Lysosomal Iron Metabolism and Membrane Permeability.Biological trace element research · 2025Article
- Lysosome-Iron-Mitochondria Axis in Osteoclasts: Iron as a Central Player.Research (Washington, D.C.) · 2025Review
- Iron-fueled ferroptosis: a new axis for immunomodulation to overcome cancer drug resistance-from immune microenvironment crosstalk to therapeutic translation.Frontiers in immunology · 2025Review
- Bile from the hemojuvelin-deficient mouse model of iron excess is enriched in iron and ferritin.Metallomics : integrated biometal science · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- A mitochondrial inside-out iron-calcium signal reveals drug targets for Parkinson's disease.Cell reports · 2023Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased brain iron content has been consistently reported in sporadic Parkinson's disease (PD) patients, and an increase in cytosolic free iron is known to cause oxidative stress and cell death. However, whether iron also accumulates in susceptible brain areas in humans or in mouse models of familial PD remains unknown. In addition, whilst the lysosome functions as a critical intracellular iron storage organelle, little is known about the mechanisms underlying lysosomal iron release and how this process is influenced by lysosome biogenesis and/or lysosomal exocytosis. Here, we report an increase in brain iron content also in PD patients due to the common G2019S-LRRK2 mutation as compared to healthy age-matched controls, whilst differences in iron content are not observed in G2019S-LRRK2 knockin as compared to control mice. Chemically triggering iron overload in cultured cells causes cytotoxicity via the endolysosomal release of iron which is mediated by TRPML1. TFEB expression reverts the iron overload-associated cytotoxicity by causing lysosomal exocytosis, which is dependent on a TRPML1-mediated increase in cytosolic calcium levels. Therefore, approaches aimed at increasing TFEB levels, or pharmacological TRPML1 activation in conjunction with iron chelation may prove beneficial against cell death associated with iron overload conditions such as those associated with PD.
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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.