ArticleBrain : a journal of neurology2022
Increased expression of SLC25A1/CIC causes an autistic-like phenotype with altered neuron morphology.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- Transcriptome profile analysis of genes by RNA-sequencing in neonatal maternal separation rats with autistic-like behaviors.Translational pediatrics · 2026Article
- Multi-omics Mendelian randomization and machine learning identify candidate therapeutic targets for Alzheimer's and Parkinson's diseases.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Increased expression of ATase1/NAT8B or ATase2/NAT8 in the mouse results in an autistic-like phenotype with altered dendritic branching and spine formation.Molecular psychiatry · 2026Article
- Overexpression of ATase1 and ATase2 disrupts the secretome and causes a progeria phenotype.Life science alliance · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- The "don't eat me" signal CD47 is associated with microglial phagocytosis defects and autism-like behaviors in 16p11.2 deletion mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CaScientific reports · 2024Article
- Spatial selectivity of ATase inhibition in mouse models of Charcot-Marie-Tooth disease.Brain communications · 2024Article
- The citrate transporters SLC13A5 and SLC25A1 elicit different metabolic responses and phenotypes in the mouse.Communications biology · 2023Article
- The Role of Proton-Coupled Amino Acid Transporter 2 (SLC36A2) in Cold-Induced Thermogenesis of Mice.Nutrients · 2023Article
- Article
- Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models.Journal of neuromuscular diseases · 2023Review
- Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
14 authors.
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Abstract
N ε-lysine acetylation within the lumen of the endoplasmic reticulum is a recently characterized protein quality control system that positively selects properly folded glycoproteins in the early secretory pathway. Overexpression of the endoplasmic reticulum acetyl-CoA transporter AT-1 in mouse forebrain neurons results in increased dendritic branching, spine formation and an autistic-like phenotype that is attributed to altered glycoprotein flux through the secretory pathway. AT-1 overexpressing neurons maintain the cytosolic pool of acetyl-CoA by upregulation of SLC25A1, the mitochondrial citrate/malate antiporter and ATP citrate lyase, which converts cytosolic citrate into acetyl-CoA. All three genes have been associated with autism spectrum disorder, suggesting that aberrant cytosolic-to-endoplasmic reticulum flux of acetyl-CoA can be a mechanistic driver for the development of autism spectrum disorder. We therefore generated a SLC25A1 neuron transgenic mouse with overexpression specifically in the forebrain neurons. The mice displayed autistic-like behaviours with a jumping stereotypy. They exhibited increased steady-state levels of citrate and acetyl-CoA, disrupted white matter integrity with activated microglia and altered synaptic plasticity and morphology. Finally, quantitative proteomic and acetyl-proteomic analyses revealed differential adaptations in the hippocampus and cortex. Overall, our study reinforces the connection between aberrant cytosolic-to-endoplasmic reticulum acetyl-CoA flux and the development of an autistic-like phenotype.
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