Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells
Abstract Mitochondrial damage and the resultant oxidative stress are associated with neurodegenerative diseases, ageing, and cancer. However, the triggers of mitochondrial damage remain unclear. We previously reported that cell-free chromatin particles (cfChPs) released from the billions of cells th...
| Үндсэн зохиолчид: | , , , , , , , |
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| Формат: | Өгүүллэг |
| Хэл сонгох: | English |
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Nature Publishing Group
2024-01-01
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| Цуврал: | Cell Death Discovery |
| Онлайн хандалт: | https://doi.org/10.1038/s41420-023-01728-z |
| _version_ | 1827377535987482624 |
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| author | Gorantla V. Raghuram Bhabesh Kumar Tripathy Kartikeya Avadhani Snehal Shabrish Naveen Kumar Khare Relestina Lopes Kavita Pal Indraneel Mittra |
| author_facet | Gorantla V. Raghuram Bhabesh Kumar Tripathy Kartikeya Avadhani Snehal Shabrish Naveen Kumar Khare Relestina Lopes Kavita Pal Indraneel Mittra |
| author_sort | Gorantla V. Raghuram |
| collection | DOAJ |
| description | Abstract Mitochondrial damage and the resultant oxidative stress are associated with neurodegenerative diseases, ageing, and cancer. However, the triggers of mitochondrial damage remain unclear. We previously reported that cell-free chromatin particles (cfChPs) released from the billions of cells that die in the body every day can readily enter healthy cells and damage their DNA. Here, we show that cfChPs isolated from the sera of healthy individuals, when applied to NIH3T3 mouse fibroblast cells, cause physical damage to mitochondrial DNA (mtDNA). cfChPs also induce ultrastructural changes, increase mitochondrial mass, alter mitochondrial shape, upregulate mitochondrial outer membrane protein translocase of the outer membrane 20, and change mitochondrial membrane potential. Furthermore, a marked increase was observed in mitochondrial superoxide (ROS) production, as detected by MitoSOX Red, and intracellular superoxide dismutase-1 activation. ROS production was also activated when a conditioned medium containing cfChPs released from hypoxia-induced dying NIH3T3 cells was applied to healthy NIH3T3 cells. ROS activation was significantly reduced when the conditioned medium was pre-treated with three different cfChP-deactivating agents: anti-histone antibody-complexed nanoparticles, DNase I, and the novel pro-oxidant combination of the nutraceuticals resveratrol and copper. Given that 1 × 109–1 × 1012 cells die in the body every day, we hypothesise that cfChPs from dying cells are the major physiological triggers for mtDNA damage and ROS production. Deactivation of cfChPs may provide a novel therapeutic approach to retard ageing and associated degenerative conditions linked to oxidative stress. |
| first_indexed | 2024-03-08T12:40:38Z |
| format | Article |
| id | doaj.art-a9cc4ee781b94e82afaa0532b25a06b0 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-08T12:40:38Z |
| publishDate | 2024-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-a9cc4ee781b94e82afaa0532b25a06b02024-01-21T12:10:36ZengNature Publishing GroupCell Death Discovery2058-77162024-01-011011910.1038/s41420-023-01728-zCell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cellsGorantla V. Raghuram0Bhabesh Kumar Tripathy1Kartikeya Avadhani2Snehal Shabrish3Naveen Kumar Khare4Relestina Lopes5Kavita Pal6Indraneel Mittra7Translational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharTranslational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharTranslational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharTranslational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharTranslational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharTranslational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharTranslational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharTranslational Research Laboratory Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, KhargharAbstract Mitochondrial damage and the resultant oxidative stress are associated with neurodegenerative diseases, ageing, and cancer. However, the triggers of mitochondrial damage remain unclear. We previously reported that cell-free chromatin particles (cfChPs) released from the billions of cells that die in the body every day can readily enter healthy cells and damage their DNA. Here, we show that cfChPs isolated from the sera of healthy individuals, when applied to NIH3T3 mouse fibroblast cells, cause physical damage to mitochondrial DNA (mtDNA). cfChPs also induce ultrastructural changes, increase mitochondrial mass, alter mitochondrial shape, upregulate mitochondrial outer membrane protein translocase of the outer membrane 20, and change mitochondrial membrane potential. Furthermore, a marked increase was observed in mitochondrial superoxide (ROS) production, as detected by MitoSOX Red, and intracellular superoxide dismutase-1 activation. ROS production was also activated when a conditioned medium containing cfChPs released from hypoxia-induced dying NIH3T3 cells was applied to healthy NIH3T3 cells. ROS activation was significantly reduced when the conditioned medium was pre-treated with three different cfChP-deactivating agents: anti-histone antibody-complexed nanoparticles, DNase I, and the novel pro-oxidant combination of the nutraceuticals resveratrol and copper. Given that 1 × 109–1 × 1012 cells die in the body every day, we hypothesise that cfChPs from dying cells are the major physiological triggers for mtDNA damage and ROS production. Deactivation of cfChPs may provide a novel therapeutic approach to retard ageing and associated degenerative conditions linked to oxidative stress.https://doi.org/10.1038/s41420-023-01728-z |
| spellingShingle | Gorantla V. Raghuram Bhabesh Kumar Tripathy Kartikeya Avadhani Snehal Shabrish Naveen Kumar Khare Relestina Lopes Kavita Pal Indraneel Mittra Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells Cell Death Discovery |
| title | Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells |
| title_full | Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells |
| title_fullStr | Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells |
| title_full_unstemmed | Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells |
| title_short | Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells |
| title_sort | cell free chromatin particles released from dying cells inflict mitochondrial damage and ros production in living cells |
| url | https://doi.org/10.1038/s41420-023-01728-z |
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