Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma
Abstract Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increa...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-91331-2 |
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| author | Kent L. Marshall Murugesan Velayutham Valery V. Khramtsov Alan Mizener Christopher P. Cifarelli |
| author_facet | Kent L. Marshall Murugesan Velayutham Valery V. Khramtsov Alan Mizener Christopher P. Cifarelli |
| author_sort | Kent L. Marshall |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3035 and U3046. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanisms in vivo. |
| format | Article |
| id | doaj-art-c5e35218fabc439f9fd74fb2e2588eb0 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-c5e35218fabc439f9fd74fb2e2588eb02025-08-20T01:57:27ZengNature PortfolioScientific Reports2045-23222025-03-0115111410.1038/s41598-025-91331-2Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastomaKent L. Marshall0Murugesan Velayutham1Valery V. Khramtsov2Alan Mizener3Christopher P. Cifarelli4Department of Neurosurgery, Rockefeller Neuroscience Institute, West Virginia UniversityDepartment of Biochemistry and Molecular Medicine, West Virginia UniversityDepartment of Biochemistry and Molecular Medicine, West Virginia UniversityWest Virginia University Cancer InstituteDepartment of Neurosurgery, Rockefeller Neuroscience Institute, West Virginia UniversityAbstract Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3035 and U3046. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanisms in vivo.https://doi.org/10.1038/s41598-025-91331-2GlioblastomaMitochondriaROSEPRRadiationCell-penetrating peptide |
| spellingShingle | Kent L. Marshall Murugesan Velayutham Valery V. Khramtsov Alan Mizener Christopher P. Cifarelli Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma Scientific Reports Glioblastoma Mitochondria ROS EPR Radiation Cell-penetrating peptide |
| title | Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma |
| title_full | Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma |
| title_fullStr | Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma |
| title_full_unstemmed | Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma |
| title_short | Enhancing radiation-induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma |
| title_sort | enhancing radiation induced reactive oxygen species generation through mitochondrial transplantation in human glioblastoma |
| topic | Glioblastoma Mitochondria ROS EPR Radiation Cell-penetrating peptide |
| url | https://doi.org/10.1038/s41598-025-91331-2 |
| work_keys_str_mv | AT kentlmarshall enhancingradiationinducedreactiveoxygenspeciesgenerationthroughmitochondrialtransplantationinhumanglioblastoma AT murugesanvelayutham enhancingradiationinducedreactiveoxygenspeciesgenerationthroughmitochondrialtransplantationinhumanglioblastoma AT valeryvkhramtsov enhancingradiationinducedreactiveoxygenspeciesgenerationthroughmitochondrialtransplantationinhumanglioblastoma AT alanmizener enhancingradiationinducedreactiveoxygenspeciesgenerationthroughmitochondrialtransplantationinhumanglioblastoma AT christopherpcifarelli enhancingradiationinducedreactiveoxygenspeciesgenerationthroughmitochondrialtransplantationinhumanglioblastoma |