Endolysosomes are key regulators of iron metabolism and are central to iron trafficking and redox signaling. Iron homeostasis is linked to endolysosome acidity and inhibition of endolysosome acidity triggers iron dysregulation. Because of the physiological importance and pathological relevance of ferrous iron (Fe ), we determined levels of Fe specifically and quantitatively in endolysosomes as well as the effects of Fe on endolysosome morphology, distribution patterns, and function. The fluorescence dye FeRhoNox-1 was specific for Fe and localized to endolysosomes in U87MG astrocytoma cells and primary rat cortical neurons; in U87MG cells the endolysosome concentration of Fe ([Fe ] ) was 50.4 μM in control cells, 73.6 μM in ferric ammonium citrate (FAC) treated cells, and 12.4 μM in cells treated with the iron chelator deferoxamine (DFO). Under control conditions, in primary rat cortical neurons, [Fe ] was 32.7 μM. Endolysosomes containing the highest levels of Fe were located perinuclearly. Treatment of cells with FAC resulted in endolysosomes that were less acidic, increased in numbers and sizes, and located further from the nucleus; opposite effects were observed for treatments with DFO. Thus, FeRhoNox-1 is a useful probe for the study of endolysosome Fe , and much more work is needed to understand better the physiological significance and pathological relevance of endolysosomes classified according to their heterogeneous iron content Cover Image for this issue: https://doi.org/10.1111/jnc.15396.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587899 | PMC |
| http://dx.doi.org/10.1111/jnc.15583 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TFEB triggers a matrix degradation and invasion program in triple-negative breast cancer cells upon mTORC1 repression.
Dev Cell
December 2024
Institut Curie, CNRS UMR 144, PSL University, 75005 Paris, France. Electronic address:
The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently hyperactivated in triple-negative breast cancers (TNBCs) associated with poor prognosis and is a therapeutic target in breast cancer management. Here, we describe the effects of repression of mTOR-containing complex 1 (mTORC1) through knockdown of several key mTORC1 components or with mTOR inhibitors used in cancer therapy. mTORC1 repression results in an ∼10-fold increase in extracellular matrix proteolytic degradation.
View Article and Find Full Text PDFDual-Engineered Phage Vaccine Platform Facilitates STING Activation for Influenza Protection.
ACS Appl Mater Interfaces
December 2024
Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362400, China.
Influenza epidemics remain a global public health challenge. Vaccination with nucleic acid-based vaccines, which trigger strong cellular and humoral immune responses, represents a promising approach for preventing virus infection. However, its effectiveness relies on efficient delivery and an immunoadjuvant.
View Article and Find Full Text PDFA multifunctional hyaluronic acid-engineered mesoporous nanoreactor with HO/O self-sufficiency for pH-triggered endo-lysosomal escape and synergetic cancer therapy.
Biomater Adv
December 2024
College of Materials Science and Engineering, Jilin Institute of Chemical Technology, Jilin City 132022, Jilin Province, PR China. Electronic address:
Monotherapy has poor accuracy and is easily restricted by tumor microenvironment (TME). Remodeling components of the TME to activate multimodal cancer therapy with high precision and efficiency is worth exploring. A multifunctional nanoreactor was fabricated by decorating chlorin e6-modified and PEGylated hyaluronic acid bearing diethylenetriamine-conjugated dihydrolipoic acid on the surface of glucose oxidase (GOx)-loaded hollow mesoporous CuS nanoparticles (labeled as GOx@HCuS@HA).
View Article and Find Full Text PDFAmodiaquine Analogs Are Potent Inhibitors of Interleukin-6 Production Induced by Activation of Toll-Like Receptors Recognizing Pathogen Nucleic Acids.
Biol Pharm Bull
December 2024
Department of Radiation Biosciences, Graduate School of Pharmaceutical Sciences, Tokyo University of Science.
Excessive inflammatory responses to viral infections, known as cytokine storms, are caused by overactivation of endolysosomal Toll-like receptors (TLRs) (TLR3, TLR7, TLR8, and TLR9) and can be lethal, but no specific treatment is available. Some quinoline derivatives with antiviral activity were tried during the recent coronavirus disease 2019 (COVID-19) pandemic, but showed serious toxicity, and their efficacy for treating viral cytokine storms was not established. Here, in order to discover a low-toxicity quinoline derivative as a candidate for controlling virally induced inflammation, we synthesized a series of derivatives of amodiaquine (ADQ), a quinoline approved as an antimalarial, and tested their effects on TLRs-mediated production of inflammatory cytokines and cell viability in vitro.
View Article and Find Full Text PDFTargeting the Ca signaling toolkit as an alternative strategy to mitigate SARS-CoV-2-induced cardiovascular adverse events.
Vascul Pharmacol
December 2024
Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy. Electronic address:
Ca signaling events are essential for maintaining cardiovascular health, regulating critical functions in both endothelial and cardiac cells. SARS-CoV-2 infection impinges this delicate balance, leading to severe cardiovascular complications. SARS-CoV-2 binds to the ACE2 receptor on endothelial and cardiomyocyte surfaces, triggering abnormal increases in intracellular Ca levels that promote endothelial dysfunction, inflammation, and hypercoagulation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!