Autism spectrum disorders: an impaired glycolysis induces an ATP deficiency and a reduced cell respiration

Abstract

In two previous studies, based on human olfactory ecto-mesenchymal stem cells (OEMSC) of 11 patients with autism spectrum disorders (ASD) and 11 healthy individuals, we demonstrated that the lower abundance of the enzyme MOCOS (MOlybdenum COfactor Sulfurase) and its associated lower expression of the long non-coding RNA, COSMOC, induces neurotransmission and synaptic defects as well as an exacerbated oxidative stress sensitivity. To move a step further, we assessed whether these defects were associated to a disturbed mitochondrial homeostasis. For that purpose, we used cellular and molecular techniques to quantify mitochondrial metabolism and biogenesis, ATP production and cell respiration in OEMSCs from the 8 ASD patients of the cohort that display the most severe symptoms. We show here that OEMSCs from ASD patients, when compared to control individuals, display i) a reduced expression/abundance of glycolysis-associated transcripts and metabolites, ii) an overall reduced ATP, mainly due to the impaired glycolysis, iii) a reduced basal cell respiration and iv) a modified mitochondrial network. These results are in accordance with some of our previously published data and may explain some of the symptoms (stress, overarousal, seizures, increased or decreased muscle tone, fatigue) observed in autism spectrum disorders.