Academic Journal
HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.
| Τίτλος: | HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors. |
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| Συγγραφείς: | Kumar N; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA.; Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, Piscataway, NJ, USA., Liang B; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA., Geiger JD; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA. |
| Πηγή: | Redox report : communications in free radical research [Redox Rep] 2026 Dec 31; Vol. 31 (1), pp. 2679333. Date of Electronic Publication: 2026 Jun 26. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 9511366 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1743-2928 (Electronic) Linking ISSN: 13510002 NLM ISO Abbreviation: Redox Rep Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2016- : Abingdon : Taylor & Francis Original Publication: Edinburgh ; New York : Churchill Livingstone, c1994- |
| Ιατρικοί όροι (MeSH): | HIV Envelope Protein gp120*/metabolism , Lysosomes*/metabolism , Transient Receptor Potential Channels*/metabolism , Transient Receptor Potential Channels*/genetics, Reactive Oxygen Species/metabolism ; Glutathione/metabolism ; HIV-1/metabolism ; Iron/metabolism ; Humans ; Oxidation-Reduction ; Cell Line, Tumor ; Oxidative Stress |
| Περίληψη: | Background: Increased lysosomal stress responses (LSR) are commonly implicated in the pathogenesis of neurodegenerative disorders including HIV-1-associated neurocognitive disorders (HAND). The HIV-1 envelope glycoprotein gp120 causes LSR, increases levels of ferrous iron (Fe2+) in the cytosol and in mitochondria, disrupts the reactive species interactome (RSI), and increases neural cell death. Methods: Using SH-SY5Y human neuroblastoma and U87MG human astrocytoma cells treated with gp120 and pharmacological modulators, we evaluated redox signaling and LSR by redox-sensitive fluorescent probes, spinning-disk confocal microscopy, flow cytometry, Western blotting, and immunostaining. Results: Here, we report that TRPML1, an endolysosome redox-sensitive cation channel, is mechanistically involved in gp120-induced neurotoxicity. TRPML1 was activated by gp120-induced increases in cytosolic reactive oxygen species (ROS) and resulted in release of Fe2+ from endolysosomes in levels sufficient to increase cytosolic levels of Fe2+ and ROS as well as decrease levels of hydrogen sulfide (H Conclusion: Our findings suggest that TRPML1 redox activation controls gp120-induced endolysosome dysfunction and iron/redox imbalance, and further implicates TRPML1 in the pathogenesis of HAND. |
| Σχόλια: | Update of: bioRxiv. 2026 Mar 04:2026.03.02.709165. doi: 10.64898/2026.03.02.709165.. (PMID: 41867743) |
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| Contributed Indexing: | Keywords: HIV-1 gp120; TRPML1; lysosomal stress responses; reactive carbonyl species; reactive nitrogen species; reactive oxygen species; reactive species interactome; reactive sulfur species; redox sensor |
| Substance Nomenclature: | 0 (HIV Envelope Protein gp120) 0 (Transient Receptor Potential Channels) 0 (Reactive Oxygen Species) 0 (MCOLN1 protein, human) GAN16C9B8O (Glutathione) 0 (gp120 protein, Human immunodeficiency virus 1) E1UOL152H7 (Iron) |
| Entry Date(s): | Date Created: 20260626 Date Completed: 20260626 Latest Revision: 20260813 |
| Update Code: | 20260814 |
| PubMed Central ID: | PMC13312838 |
| DOI: | 10.1080/13510002.2026.2679333 |
| PMID: | 42359813 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1743-2928 |
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| DOI: | 10.1080/13510002.2026.2679333 |