Abnormalities of synaptic mitochondria in autism spectrum disorder and related neurodevelopmental disorders
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REVIEW
Abnormalities of synaptic mitochondria in autism spectrum disorder and related neurodevelopmental disorders Liliana Rojas-Charry 1,2,3 & Leonardo Nardi 1 & Axel Methner 2,3 & Michael J. Schmeisser 1,3 Received: 3 September 2020 / Revised: 27 November 2020 / Accepted: 2 December 2020 # The Author(s) 2020
Abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition primarily characterized by an impairment of social interaction combined with the occurrence of repetitive behaviors. ASD starts in childhood and prevails across the lifespan. The variability of its clinical presentation renders early diagnosis difficult. Mutations in synaptic genes and alterations of mitochondrial functions are considered important underlying pathogenic factors, but it is obvious that we are far from a comprehensive understanding of ASD pathophysiology. At the synapse, mitochondria perform diverse functions, which are clearly not limited to their classical role as energy providers. Here, we review the current knowledge about mitochondria at the synapse and summarize the mitochondrial disturbances found in mouse models of ASD and other ASD-related neurodevelopmental disorders, like DiGeorge syndrome, Rett syndrome, Tuberous sclerosis complex, and Down syndrome. Keywords Autism spectrum disorder . ASD . Synapse . Mitochondria . Neurodevelopmental disorders
Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition that starts in childhood and prevails across the lifespan, symptoms are variable, and a substantial increase in ASD diagnosis has been reported during the last 40 years [1]. A significant part of ASD cases is associated with mutations in synaptic proteins, suggesting an impairment of synaptic transmission as a primary underlying cause [2–7]. Synaptic activity is an energetically expensive process that consumes a large proportion of the adenosine triphosphate (ATP) generated in neurons, which is mainly produced by mitochondria through
* Axel Methner [email protected] * Michael J. Schmeisser [email protected] 1
Institute for Microscopic Anatomy and Neurobiology, University Medical Center of the Johannes Gutenberg-University, Duesbergweg 6, 55128 Mainz, Germany
2
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstraße 1, 55131 Mainz, Germany
3
Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
oxidative phosphorylation (OXPHOS) [8]. Mitochondria are present in approximately half of all presynaptic boutons, and synapses that contain mitochondria have more vesicles [9]. Postsynaptic mitochondria are less abundant and have a more tubular form than presynaptic mitochondria [10], indicating that distinct morphological changes in dendrites and axons occur to adjust their shape to energetic or other needs [11]. In addition, local synthesis of new proteins occurs in axons and dendrites and depends on mitochondria that provide energy during synaptic
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