Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated manner
Inflammation is associated with a wide range of medical conditions, most leading causes of death, and high healthcare costs. It can thus benefit from new insights. Here we extended previous studies and found that oxidation of human native mtRNA to ‘mitoxRNA’ strongly potentiated IFNβ and TNFα immuno...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Redox Report |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2025.2491845 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850149826817163264 |
|---|---|
| author | Hung-Yun Lin Ramon B. Ramos Dana R. Crawford |
| author_facet | Hung-Yun Lin Ramon B. Ramos Dana R. Crawford |
| author_sort | Hung-Yun Lin |
| collection | DOAJ |
| description | Inflammation is associated with a wide range of medical conditions, most leading causes of death, and high healthcare costs. It can thus benefit from new insights. Here we extended previous studies and found that oxidation of human native mtRNA to ‘mitoxRNA’ strongly potentiated IFNβ and TNFα immunostimulation in human cells, and that this newly identified type 1 interferon potentiation was transcriptional. This potentiation was significantly greater than with mtDNA oxidation, and t-butylhydroperoxide (tBHP) oxidation of RNA was more proinflammatory than hydrogen peroxide (HP). mtRNA triggered a modest increase in apoptosis that was not potentiated by oxidation, and mtDNA triggered a much greater increase. For native mtRNA, we found that chloroquine-inhibitable endosomes and MDA5 are key signaling pathways for IFNβ and TNFα production. For mitoxRNAs, RNAseq revealed a major increase in both tBHP- and HP-mitoxRNA modulated genes compared with native mtRNA. This increase was very prominent for interferon-related genes, identifying them as important mediators of this powerful oxidation effect. Moderately different gene modulations and KEGG pathways were observed for tBHP- versus HP-mitoxRNAs. These studies reveal the profound effect that mitochondrial RNA oxidation has on immunostimulation, providing new insights into DAMP inflammation and identifying potential therapeutic targets to minimize DAMP mtRNA/mitoxRNA-mediated inflammation. |
| format | Article |
| id | doaj-art-09c7a82161284dfcad1312fc4c93bb9b |
| institution | OA Journals |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj-art-09c7a82161284dfcad1312fc4c93bb9b2025-08-20T02:26:46ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2491845Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated mannerHung-Yun Lin0Ramon B. Ramos1Dana R. Crawford2Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USADepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USAInflammation is associated with a wide range of medical conditions, most leading causes of death, and high healthcare costs. It can thus benefit from new insights. Here we extended previous studies and found that oxidation of human native mtRNA to ‘mitoxRNA’ strongly potentiated IFNβ and TNFα immunostimulation in human cells, and that this newly identified type 1 interferon potentiation was transcriptional. This potentiation was significantly greater than with mtDNA oxidation, and t-butylhydroperoxide (tBHP) oxidation of RNA was more proinflammatory than hydrogen peroxide (HP). mtRNA triggered a modest increase in apoptosis that was not potentiated by oxidation, and mtDNA triggered a much greater increase. For native mtRNA, we found that chloroquine-inhibitable endosomes and MDA5 are key signaling pathways for IFNβ and TNFα production. For mitoxRNAs, RNAseq revealed a major increase in both tBHP- and HP-mitoxRNA modulated genes compared with native mtRNA. This increase was very prominent for interferon-related genes, identifying them as important mediators of this powerful oxidation effect. Moderately different gene modulations and KEGG pathways were observed for tBHP- versus HP-mitoxRNAs. These studies reveal the profound effect that mitochondrial RNA oxidation has on immunostimulation, providing new insights into DAMP inflammation and identifying potential therapeutic targets to minimize DAMP mtRNA/mitoxRNA-mediated inflammation.https://www.tandfonline.com/doi/10.1080/13510002.2025.2491845Mitochondriaoxidative stressT-butylhydroperoxidehydrogen peroxidetype 1 interferonsproinflammatory cytokines |
| spellingShingle | Hung-Yun Lin Ramon B. Ramos Dana R. Crawford Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated manner Redox Report Mitochondria oxidative stress T-butylhydroperoxide hydrogen peroxide type 1 interferons proinflammatory cytokines |
| title | Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated manner |
| title_full | Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated manner |
| title_fullStr | Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated manner |
| title_full_unstemmed | Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated manner |
| title_short | Oxidation of human mitochondrial RNA strongly potentiates immunostimulation in an interferon-associated manner |
| title_sort | oxidation of human mitochondrial rna strongly potentiates immunostimulation in an interferon associated manner |
| topic | Mitochondria oxidative stress T-butylhydroperoxide hydrogen peroxide type 1 interferons proinflammatory cytokines |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2025.2491845 |
| work_keys_str_mv | AT hungyunlin oxidationofhumanmitochondrialrnastronglypotentiatesimmunostimulationinaninterferonassociatedmanner AT ramonbramos oxidationofhumanmitochondrialrnastronglypotentiatesimmunostimulationinaninterferonassociatedmanner AT danarcrawford oxidationofhumanmitochondrialrnastronglypotentiatesimmunostimulationinaninterferonassociatedmanner |