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Journal article
Heterogeneity of ferrous iron-containing endolysosomes and effects of endolysosome iron on endolysosome numbers, sizes, and localization patterns
Journal of neurochemistry, v 161(1)
01 Apr 2022
PMID: 35124818
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 (Fe2+), we determined levels of Fe2+ specifically and quantitatively in endolysosomes as well as the effects of Fe2+ on endolysosome morphology, distribution patterns, and function. The fluorescence dye FeRhoNox-1 was specific for Fe2+ and localized to endolysosomes in U87MG astrocytoma cells and primary rat cortical neurons; in U87MG cells the endolysosome concentration of Fe2+ ([Fe2+](el)) was 50.4 mu M in control cells, 73.6 mu M in ferric ammonium citrate (FAC) treated cells, and 12.4 mu M in cells treated with the iron chelator deferoxamine (DFO). Under control conditions, in primary rat cortical neurons, [Fe2+](el) was 32.7 mu M. Endolysosomes containing the highest levels of Fe2+ 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 Fe2+, and much more work is needed to understand better the physiological significance and pathological relevance of endolysosomes classified according to their heterogeneous iron content.
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- Title
- Heterogeneity of ferrous iron-containing endolysosomes and effects of endolysosome iron on endolysosome numbers, sizes, and localization patterns
- Creators
- Peter W. Halcrow - University of North DakotaNirmal Kumar - University of North DakotaZahra Afghah - University of North DakotaJalyn P. Fischer - University of North DakotaNabab Khan - University of North DakotaXuesong Chen - University of North DakotaOlimpia Meucci - Drexel UniversityJonathan D. Geiger - University of North Dakota
- Publication Details
- Journal of neurochemistry, v 161(1)
- Publisher
- Wiley
- Number of pages
- 15
- Grant note
- P30GM100329; U54GM115458 / National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 2R01DA032444 / National Institute of Drug Abuse; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) R01MH100972; R01MH105329; R01MH119000 / National Institute of Mental Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) 2R01NS065957 / National Institute of Neurological Diseases and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000770056600006
- Scopus ID
- 2-s2.0-85125067126
- Other Identifier
- 991019167854704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences