Background: A diverse array of data has been associated with autism spectrum disorder (ASD), reflecting
the complexity of its pathophysiology as well as its heterogeneity. Two important hubs have emerged, the
placenta/prenatal period and the postnatal gut, with alterations in mitochondria functioning crucial in both.
Methods: Factors acting to regulate mitochondria functioning in ASD across development are reviewed in this
Results: Decreased vitamin A, and its retinoic acid metabolites, lead to a decrease in CD38 and associated
changes that underpin a wide array of data on the biological underpinnings of ASD, including decreased oxytocin,
with relevance both prenatally and in the gut. Decreased sirtuins, poly-ADP ribose polymerase-driven decreases
in nicotinamide adenine dinucleotide (NAD+), hyperserotonemia, decreased monoamine oxidase, alterations in
14-3-3 proteins, microRNA alterations, dysregulated aryl hydrocarbon receptor activity, suboptimal mitochondria
functioning, and decreases in the melatonergic pathways are intimately linked to this. Many of the above processes
may be modulating, or mediated by, alterations in mitochondria functioning. Other bodies of data associated
with ASD may also be incorporated within these basic processes, including how ASD risk factors such as maternal
obesity and preeclampsia, as well as more general prenatal stressors, modulate the likelihood of offspring
Conclusion: Such a mitochondria-focussed integrated model of the pathophysiology of ASD has important preventative
and treatment implications.