Abstract
We propose that the mitochondrion, an essential cellular organelle, mediates the long-term prenatal environmental effects of disease in autism spectrum disorder (ASD). Many prenatal environmental factors which increase the risk of developing ASD influence mitochondria physiology, including toxicant exposures, immune activation, and nutritional factors. Unique types of mitochondrial dysfunction have been associated with ASD and recent studies have linked prenatal environmental exposures to long-term changes in mitochondrial physiology in children with ASD. A better understanding of the role of the mitochondria in the etiology of ASD can lead to targeted therapeutics and strategies to potentially prevent the development of ASD.
Highlights
Autism spectrum disorder (ASD) is a behaviorally defined disorder [1], with the most recent Center for Disease Control and Prevention estimates suggesting that it affects 1 in 54 children in the United States [2]
The possibility that environmentally induced mitochondrial dysfunction could have a role in ASD is compelling because abnormal mitochondrial function is one of the most prevalent metabolic disorders found in individuals with ASD, with prevalence ranging from 5% for classically defined mitochondrial disease to 8–47% for biomarkers of mitochondrial dysfunction [11,16], to 62–65% for abnormal electron transport chain (ETC)/citric acid cycle (CAC) enzymology [93,94], and to 80% for abnormal ETC activity in lymphocytes and granulocytes [95,96]
The first case reported was a boy with ASD who demonstrated a significant increase in ETC complex I activity while his sister, who was diagnosed with a classic mitochondrial disease known as Leigh syndrome, showed depressed ETC activity [97]
Summary
Autism spectrum disorder (ASD) is a behaviorally defined disorder [1], with the most recent Center for Disease Control and Prevention estimates suggesting that it affects 1 in 54 children in the United States [2]. Recent studies suggest that inherited single-gene and chromosomal defects account for a minority of ASD cases [3], and that ASD most likely arises from a complicated interaction between genetic predisposition and environmental exposures [4,5]. Despite the epidemiological connection between many prenatal risk factors and the development of ASD, the biological mechanisms which link prenatal environmental influences and the increased risk of developing ASD are just beginning to be uncovered. Three physiological abnormalities which have been increasingly recognized to be associated with ASD are immune system dysfunction, mitochondrial dysfunction, and oxidative stress and redox regulation [1]. Previous reviews examining prenatal physiological abnormalities related to ASD have concentrated on prenatal immune stressors as key and consider mitochondrial dysfunction and oxidative stress to have secondary roles of this “Bad Trio” [8]. The particular component of the “Bad Trio” that is the initiating culprit may be different for different patients and it is possible that multiple stressors on the various portions of the “Bad Trio” simultaneously may initiate the pathway to disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
