OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress
Abstract Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well as in stroke. However, our knowledge of the genetic elements that can be manipulated to protect neurons from oxidative stress-ind...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55105-0 |
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| author | Alessandra Donato Fiona K. Ritchie Lachlan Lu Mehershad Wadia Ramon Martinez-Marmol Eva Kaulich Kornraviya Sankorrakul Hang Lu Sean Coakley Elizabeth J. Coulson Massimo A. Hilliard |
| author_facet | Alessandra Donato Fiona K. Ritchie Lachlan Lu Mehershad Wadia Ramon Martinez-Marmol Eva Kaulich Kornraviya Sankorrakul Hang Lu Sean Coakley Elizabeth J. Coulson Massimo A. Hilliard |
| author_sort | Alessandra Donato |
| collection | DOAJ |
| description | Abstract Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well as in stroke. However, our knowledge of the genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death is still very limited. Here, using Caenorhabditis elegans as a model system, combined with the optogenetic tool KillerRed to spatially and temporally control ROS generation, we identify a previously uncharacterized gene, oxidative stress protective 1 (osp-1), that protects C. elegans neurons from oxidative damage. Using rodent and human cell cultures, we also show that the protective effect of OSP-1 extends to mammalian cells. Moreover, we demonstrate that OSP-1 functions in a strictly cell-autonomous fashion, and that it localizes to the endoplasmic reticulum (ER) where it has an ER-remodeling function. Finally, we present evidence suggesting that OSP-1 may exert its neuroprotective function by influencing autophagy. Our results point to a potential role of OSP-1 in modulating autophagy, and suggest that overactivation of this cellular process could contribute to neuronal death triggered by oxidative damage. |
| format | Article |
| id | doaj-art-5d5e52e361084101ad6eb9c54ead7d23 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5d5e52e361084101ad6eb9c54ead7d232025-01-05T12:41:07ZengNature PortfolioNature Communications2041-17232025-01-0116111910.1038/s41467-024-55105-0OSP-1 protects neurons from autophagic cell death induced by acute oxidative stressAlessandra Donato0Fiona K. Ritchie1Lachlan Lu2Mehershad Wadia3Ramon Martinez-Marmol4Eva Kaulich5Kornraviya Sankorrakul6Hang Lu7Sean Coakley8Elizabeth J. Coulson9Massimo A. Hilliard10Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandSchool of Biomedical Sciences, Faculty of Medicine, The University of QueenslandSchool of Chemical & Biomolecular Engineering, Georgia Institute of TechnologySchool of Biomedical Sciences, Faculty of Medicine, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandAbstract Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well as in stroke. However, our knowledge of the genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death is still very limited. Here, using Caenorhabditis elegans as a model system, combined with the optogenetic tool KillerRed to spatially and temporally control ROS generation, we identify a previously uncharacterized gene, oxidative stress protective 1 (osp-1), that protects C. elegans neurons from oxidative damage. Using rodent and human cell cultures, we also show that the protective effect of OSP-1 extends to mammalian cells. Moreover, we demonstrate that OSP-1 functions in a strictly cell-autonomous fashion, and that it localizes to the endoplasmic reticulum (ER) where it has an ER-remodeling function. Finally, we present evidence suggesting that OSP-1 may exert its neuroprotective function by influencing autophagy. Our results point to a potential role of OSP-1 in modulating autophagy, and suggest that overactivation of this cellular process could contribute to neuronal death triggered by oxidative damage.https://doi.org/10.1038/s41467-024-55105-0 |
| spellingShingle | Alessandra Donato Fiona K. Ritchie Lachlan Lu Mehershad Wadia Ramon Martinez-Marmol Eva Kaulich Kornraviya Sankorrakul Hang Lu Sean Coakley Elizabeth J. Coulson Massimo A. Hilliard OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress Nature Communications |
| title | OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress |
| title_full | OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress |
| title_fullStr | OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress |
| title_full_unstemmed | OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress |
| title_short | OSP-1 protects neurons from autophagic cell death induced by acute oxidative stress |
| title_sort | osp 1 protects neurons from autophagic cell death induced by acute oxidative stress |
| url | https://doi.org/10.1038/s41467-024-55105-0 |
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