Abstract

Front cover Endolysosomes are central to iron trafficking and redox signaling. Iron homeostasis is linked to endolysosome acidity and inhibition of endolysosome acidity triggers iron dysregulation. With view to the physiological and pathological relevance of ferrous iron (Fe2+), we determined 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 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). 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 size, 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+. Image content Primary neuron demonstrating endolysosome ferrous iron (yellow puncta). Read the full article ‘Heterogeneity of ferrous iron-containing endolysosomes and effects of endolysosome iron on endolysosome numbers, sizes, and localization patterns’ by P. W. Halcrow, N. Kumar, Z. Afghah, J. P. Fischer, N. Khan, X. Chen, O. Meucci and J. D. Geiger (J. Neurochem. 2022, vol. 161 (1), pp. 69–83) on doi:10.1111/jnc.15583

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