Defining the Role of Mitochondrial Dysfunction in Autism Spectrum Disorder
Final Report Abstract
The etiology of autism spectrum disorders (ASD) remains unknown. Although synaptic genes represent the best candidates for the pathogenesis of ASD, the complexity of these disorders implies that other cellular functions are compromised. A good example is the increased prevalence of mitochondrial disease in cohorts of individuals with ASD. Mitochondria participate in several biological processes involving classical energy production, calcium buffering, cell death signaling, hormone production, and redox homeostasis. In this study, I hypothesized that ASD alters mitochondrial bioenergetics, synaptic redox, and metabolic states. I assessed mitochondrial respiration with high-resolution respirometry in different brain regions of ASD mice. I simultaneously measured the production of reactive oxygen species (ROS) and evaluated mitochondrial morphology with electron microscopy. I found functional and morphological mitochondrial impairments characterized by reduced respiration in the striatum of ASD mice, more fragmented mitochondria, and reduced mitochondria-endoplasmic-reticulum (ER) contact sites. Redox proteomic analysis identified an enhanced redox state in the striatum ASD mice. These results demonstrate that mitochondrial functional and redox impairments are present in ASD mice in the striatum and highlight the importance of energy balance in ASD pathology.
Publications
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Synaptic mitochondrial impairments are involved in autism spectrum disorder. International Neurochemistry Conference, Faro, Portugal: poster presentation.
Rojas-Charry, Liliana
