Journal article
Involvement of endolysosome iron in HIV-1 gp120-, morphine-, and iron supplementation-induced disruption of the reactive species interactome and induction of neurotoxicity
Redox report : communications in free radical research, v 30(1), 2546496
31 Dec 2025
PMID: 40839751
Featured in Collection : Drexel's Newest Publications
Abstract
Background: Iron continues to be linked to the pathogenesis of neurodegenerative disorders including HIV-1 associated neurocognitive disorders (HAND). People with HIV-1 who use opioids have a higher risk of developing HAND, and HIV-1 proteins and opioids disrupt endolysosome iron homeostasis, increase reactive oxygen species (ROS), and cause neural cell death. Endolysosomes are subcellular acidic organelles that regulate iron metabolism and redox homeostasis. HIV-1 gp120 and opioids induce endolysosome iron release, increasing cytosolic and in mitochondrial iron and ROS and inducing neurotoxicity. However, ROS represent only part of the reactive species interactome (RSI) and little is known about the extent to which HIV-1 proteins and opioids affect the RSI. Results: In SH-SY5Y and U87MG cells, HIV-1 gp120, morphine, and iron supplementation de-acidified endolysosomes, decreased endolysosome Fe
2+
and H
2
S, and increased ROS, lipid peroxidation (LPO) and NO. These changes were accompanied by increased cytosolic and mitochondrial Fe
2+
, ROS, LPO, and NO, decreased H
2
S, and increased cell death. All effects were blocked by the endolysosome-specific iron chelator deferoxamine. Conclusion: Endolysosome iron dyshomeostasis induced by HIV-1 gp120, morphine and iron supplementation disrupts inter-organellar iron signaling and RSI homeostasis. Targeting endolysosome iron may mitigate neurotoxicity in HAND and other disorders associated with iron overload and redox imbalance.
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Details
- Title
- Involvement of endolysosome iron in HIV-1 gp120-, morphine-, and iron supplementation-induced disruption of the reactive species interactome and induction of neurotoxicity
- Creators
- Nirmal Kumar - University of North DakotaPeter W. Halcrow - University of North DakotaDarius N. K. Quansah - University of North DakotaBraelyn Liang - University of North DakotaOlimpia Meucci - Drexel UniversityJonathan D. Geiger - University of North Dakota
- Publication Details
- Redox report : communications in free radical research, v 30(1), 2546496
- Publisher
- Taylor & Francis
- Number of pages
- 21
- Grant note
- National Institute of General Medical Sciences: P20GM139759 National Institute of Mental Health: R01MH119000 National Institute of Neurological Disorders and Stroke: 2R01NS065957 National Institute on Drug Abuse: 2R01DA032444
We gratefully acknowledge support from the National Institute of General Medical Sciences [P20GM139759]; the National Institute of Mental Health [R01MH119000]; the National Institute of Neurological Disorders and Stroke [2R01NS065957]; and the National Institute on Drug Abuse [2R01DA032444].
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001554871200001
- Scopus ID
- 2-s2.0-105013875634
- Other Identifier
- 991022084626304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology