Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms
Oxid Med Cell Longev. 2017 May 29.
Keren K. Griffiths and Richard J. Levy
Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA
Abstract
Autism spectrum disorder (ASD), the fastest growing developmental disability in the United States, represents a group of neurodevelopmental disorders characterized by impaired social interaction and communication as well as restricted and repetitive behavior. The underlying cause of autism is unknown and therapy is currently limited to targeting behavioral abnormalities. Emerging studies suggest a link between mitochondrial dysfunction and ASD. Here, we review the evidence demonstrating this potential connection. We focus specifically on biochemical links, genetic-based associations, non-energy related mechanisms, and novel therapeutic strategies.
Conclusion The literature reviewed here suggests a link between abnormalities in mitochondrial homeostasis and ASD and provides biochemical and genetic evidence to support a role for mitochondrial dysfunction in the pathogenesis of the autism phenotype. Mechanistically, the connection may involve defects in bioenergetic capacity as well as non-energy related pathways. However, it is not clear if mitochondrial impairments cause ASD or if they are merely associated with the disease process. Positive patient behavioral responses to conventional mitochondrial disease therapies are promising, however, further investigation is necessary. Future work should focus on determining how mitochondrial dysfunction causes the autistic phenotype as well as how defects in mitochondrial homeostasis predispose individuals to ASD via interaction with environmental toxins, dietary factors, and epigenetic modifications during critical periods of development. Establishing a causative relationship between mitochondrial dysfunction and ASD and elucidating the exact mechanisms will permit the development of more precisely targeted therapies in the future. Ultimately, with improved knowledge and innovation, we may one day be able to prevent or cure autism.
