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Article

Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with Shank3 Mutation Associated with Autism Spectrum Disorder

Faculty of Medicine, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
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Author to whom correspondence should be addressed.
Academic Editors: Eugenio Aguglia and Laura Fusar-Poli
Brain Sci. 2021, 11(6), 677; https://doi.org/10.3390/brainsci11060677
Received: 13 April 2021 / Revised: 17 May 2021 / Accepted: 19 May 2021 / Published: 21 May 2021
(This article belongs to the Special Issue Understanding 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 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 Shank3 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 Shank3 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 Shank3 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. View Full-Text
Keywords: autism spectrum disorder; nitric oxide; S-nitrosylation; proteomics mitochondria; systems biology autism spectrum disorder; nitric oxide; S-nitrosylation; proteomics mitochondria; systems biology
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MDPI and ACS Style

Kartawy, M.; Khaliulin, I.; Amal, H. Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with Shank3 Mutation Associated with Autism Spectrum Disorder. Brain Sci. 2021, 11, 677. https://doi.org/10.3390/brainsci11060677

AMA Style

Kartawy M, Khaliulin I, Amal H. Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with Shank3 Mutation Associated with Autism Spectrum Disorder. Brain Sciences. 2021; 11(6):677. https://doi.org/10.3390/brainsci11060677

Chicago/Turabian Style

Kartawy, Maryam; Khaliulin, Igor; Amal, Haitham. 2021. "Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with Shank3 Mutation Associated with Autism Spectrum Disorder" Brain Sci. 11, no. 6: 677. https://doi.org/10.3390/brainsci11060677

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