Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxia
Abstract This study investigated the roles and mechanisms of PINK1 activity in neonatal hypoxia-induced seizures with shRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7), the positive regulator of PINK1 autophosphorylation, or overlapping with the m-AAA protease 1 homolog...
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| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-99915-8 |
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| author | Yi Yuan Xiaoqian Wang Yaru Cui Hua Zhou Wenna Li Qian Teng Hongjin Wang Bohan Sun Qiaoyun Wang Hongliu Sun Jianhua Tang |
| author_facet | Yi Yuan Xiaoqian Wang Yaru Cui Hua Zhou Wenna Li Qian Teng Hongjin Wang Bohan Sun Qiaoyun Wang Hongliu Sun Jianhua Tang |
| author_sort | Yi Yuan |
| collection | DOAJ |
| description | Abstract This study investigated the roles and mechanisms of PINK1 activity in neonatal hypoxia-induced seizures with shRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7), the positive regulator of PINK1 autophosphorylation, or overlapping with the m-AAA protease 1 homolog (OMA1), the negative regulator of PINK1 autophosphorylation. Studies have suggested that in hypoxia-induced neonatal seizures, the phosphorylation level of PINK1 is significantly increased and the mitophagic pathway is activated, accompanied by neuronal damage and learning-memory deficits. Inhibiting PINK1 phosphorylation by reducing TOM7 expression alleviated mitophagy, mitochondrial oxidative stress, neuronal damage and seizures. In contrast, the inhibition of OMA1 expression resulted in a further increase in PINK1 phosphorylation and aggravated hypoxia-induced seizures and neuronal injury. This study implicated PINK1 activity in neonatal hypoxia and suggest that attenuated PINK1 autophosphorylation may have neuroprotective and anti-seizure effects in neonatal hypoxia. |
| format | Article |
| id | doaj-art-5a2c3497d0854f4e8dc399fea1b856cd |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5a2c3497d0854f4e8dc399fea1b856cd2025-08-20T02:10:50ZengNature PortfolioScientific Reports2045-23222025-04-0115111510.1038/s41598-025-99915-8Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxiaYi Yuan0Xiaoqian Wang1Yaru Cui2Hua Zhou3Wenna Li4Qian Teng5Hongjin Wang6Bohan Sun7Qiaoyun Wang8Hongliu Sun9Jianhua Tang10School of Pharmaceutical Sciences, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversityAffiliated Yantai Mountain Hospital, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversitySchool of Pharmaceutical Sciences, Binzhou Medical UniversityAffiliated Yantai Mountain Hospital, Binzhou Medical UniversityAbstract This study investigated the roles and mechanisms of PINK1 activity in neonatal hypoxia-induced seizures with shRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7), the positive regulator of PINK1 autophosphorylation, or overlapping with the m-AAA protease 1 homolog (OMA1), the negative regulator of PINK1 autophosphorylation. Studies have suggested that in hypoxia-induced neonatal seizures, the phosphorylation level of PINK1 is significantly increased and the mitophagic pathway is activated, accompanied by neuronal damage and learning-memory deficits. Inhibiting PINK1 phosphorylation by reducing TOM7 expression alleviated mitophagy, mitochondrial oxidative stress, neuronal damage and seizures. In contrast, the inhibition of OMA1 expression resulted in a further increase in PINK1 phosphorylation and aggravated hypoxia-induced seizures and neuronal injury. This study implicated PINK1 activity in neonatal hypoxia and suggest that attenuated PINK1 autophosphorylation may have neuroprotective and anti-seizure effects in neonatal hypoxia.https://doi.org/10.1038/s41598-025-99915-8PINK1MitophagySeizureNeuronal injuryMitochondrial oxidative stress |
| spellingShingle | Yi Yuan Xiaoqian Wang Yaru Cui Hua Zhou Wenna Li Qian Teng Hongjin Wang Bohan Sun Qiaoyun Wang Hongliu Sun Jianhua Tang Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxia Scientific Reports PINK1 Mitophagy Seizure Neuronal injury Mitochondrial oxidative stress |
| title | Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxia |
| title_full | Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxia |
| title_fullStr | Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxia |
| title_full_unstemmed | Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxia |
| title_short | Attenuated PINK1 autophosphorylation play neuroprotective and anti-seizure roles in neonatal hypoxia |
| title_sort | attenuated pink1 autophosphorylation play neuroprotective and anti seizure roles in neonatal hypoxia |
| topic | PINK1 Mitophagy Seizure Neuronal injury Mitochondrial oxidative stress |
| url | https://doi.org/10.1038/s41598-025-99915-8 |
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