Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a neurodevelopmental disorder manifested in repetitive behavior, abnormalities in social interactions, and communication. The pathogenesis of this disorder is not clear, and no effective treatment is currently available. Protein S-nitrosylation (SNO), the nitric oxi...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/11/6/677 |
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| author | Maryam Kartawy Igor Khaliulin Haitham Amal |
| author_facet | Maryam Kartawy Igor Khaliulin Haitham Amal |
| author_sort | Maryam Kartawy |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) is a neurodevelopmental disorder manifested in repetitive behavior, abnormalities in social interactions, and communication. The pathogenesis of this disorder is not clear, and no effective treatment is currently available. Protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification, targets key proteins implicated in synaptic and neuronal functions. Previously, we have shown that NO and SNO are involved in the ASD mouse model based on the <i>Shank3</i> mutation. The energy supply to the brain mostly relies on oxidative phosphorylation in the mitochondria. Recent studies show that mitochondrial dysfunction and oxidative stress are involved in ASD pathology. In this work, we performed SNO proteomics analysis of cortical tissues of the <i>Shank3</i> mouse model of ASD with the focus on mitochondrial proteins and processes. The study was based on the SNOTRAP technology followed by systems biology analysis. This work revealed that 63 mitochondrial proteins were S-nitrosylated and that several mitochondria-related processes, including those associated with oxidative phosphorylation, oxidative stress, and apoptosis, were enriched. This study implies that aberrant SNO signaling induced by the <i>Shank3</i> mutation can target a wide range of mitochondria-related proteins and processes that may contribute to the ASD pathology. It is the first study to investigate the role of NO-dependent mitochondrial functions in ASD. |
| first_indexed | 2024-03-10T11:10:22Z |
| format | Article |
| id | doaj.art-757a180215f346bc8597aa0147fcb1fa |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T11:10:22Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-757a180215f346bc8597aa0147fcb1fa2023-11-21T20:50:58ZengMDPI AGBrain Sciences2076-34252021-05-0111667710.3390/brainsci11060677Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum DisorderMaryam Kartawy0Igor Khaliulin1Haitham Amal2Faculty of Medicine, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelFaculty of Medicine, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelFaculty of Medicine, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelAutism spectrum disorder (ASD) is a neurodevelopmental disorder manifested in repetitive behavior, abnormalities in social interactions, and communication. The pathogenesis of this disorder is not clear, and no effective treatment is currently available. Protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification, targets key proteins implicated in synaptic and neuronal functions. Previously, we have shown that NO and SNO are involved in the ASD mouse model based on the <i>Shank3</i> mutation. The energy supply to the brain mostly relies on oxidative phosphorylation in the mitochondria. Recent studies show that mitochondrial dysfunction and oxidative stress are involved in ASD pathology. In this work, we performed SNO proteomics analysis of cortical tissues of the <i>Shank3</i> mouse model of ASD with the focus on mitochondrial proteins and processes. The study was based on the SNOTRAP technology followed by systems biology analysis. This work revealed that 63 mitochondrial proteins were S-nitrosylated and that several mitochondria-related processes, including those associated with oxidative phosphorylation, oxidative stress, and apoptosis, were enriched. This study implies that aberrant SNO signaling induced by the <i>Shank3</i> mutation can target a wide range of mitochondria-related proteins and processes that may contribute to the ASD pathology. It is the first study to investigate the role of NO-dependent mitochondrial functions in ASD.https://www.mdpi.com/2076-3425/11/6/677autism spectrum disordernitric oxideS-nitrosylationproteomics mitochondriasystems biology |
| spellingShingle | Maryam Kartawy Igor Khaliulin Haitham Amal Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum Disorder Brain Sciences autism spectrum disorder nitric oxide S-nitrosylation proteomics mitochondria systems biology |
| title | Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum Disorder |
| title_full | Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum Disorder |
| title_fullStr | Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum Disorder |
| title_full_unstemmed | Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum Disorder |
| title_short | Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with <i>Shank3</i> Mutation Associated with Autism Spectrum Disorder |
| title_sort | systems biology reveals s nitrosylation dependent regulation of mitochondrial functions in mice with i shank3 i mutation associated with autism spectrum disorder |
| topic | autism spectrum disorder nitric oxide S-nitrosylation proteomics mitochondria systems biology |
| url | https://www.mdpi.com/2076-3425/11/6/677 |
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