Mitochondrial Dysfunction in Autism – Source: JAMA, Dec 1, 2010

1 Star2 Stars3 Stars4 Stars5 Stars (7 votes, average: 3.55 out of 5)
Loading...

Context: Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism. [Mitochondria are structures in cells that convert energy from food into fuel for the cells. Mitochondria have their own DNA, containing 37 genes needed for them to function normally.]

Objective: To evaluate mitochondrial defects in children with autism.

Design, Setting, and Patients: Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood Autism Risk From Genes and Environment [CHARGE] study in California, which is a population-based, case-control investigation with confirmed autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing.

Mitochondrial dysfunction and mitochondrial DNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls.

Main Outcome Measures: Oxidative phosphorylation capacity, mitochondrial DNA copy number and deletions, mitochondrial rate of hydrogen peroxide production, and plasma lactate and pyruvate. [Oxidative phosphorylation is driven by 13 of the mitochondrial DNA genes. It is a process that uses oxygen and simple sugars to create ATP, the cell's main energy source.]

Results: The reduced nicotinamide adenine dinucleotide (NADH) oxidase activity (normalized to citrate synthase activity) in lymphocytic mitochondria from children with autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001).

The majority of children with autism (6 of 10) had complex I activity below control range values.

Higher plasma pyruvate levels were found in children with autism compared with controls (0.23 mM [95% CI, 0.15-0.31 mM] vs 0.08 mM [95% CI, 0.04-0.12 mM], respectively; P = .02).

Eight of 10 cases had higher pyruvate levels but only 2 cases had higher lactate levels compared with controls.

These results were consistent with the lower pyruvate dehydrogenase activity observed in children with autism compared with controls (1.0 [95% CI, 0.6-1.4] nmol × [min × mg protein]?1 vs 2.3 [95% CI, 1.7-2.9] nmol × [min × mg protein]?1, respectively; P = .01).

Children with autism had higher mitochondrial rates of hydrogen peroxide production compared with controls (0.34 [95% CI, 0.26-0.42] nmol × [min × mg of protein]-1 vs 0.16 [95% CI, 0.12-0.20] nmol × [min × mg protein]-1 by complex III; P = .02).

Mitochondrial DNA overreplication was found in 5 cases (mean ratio of mtDNA to nuclear DNA: 239 [95% CI, 217-239] vs 179 [95% CI, 165-193] in controls; P = 10-4).

Deletions at the segment of cytochrome b were observed in 2 cases (ratio of cytochrome b to ND1: 0.80 [95% CI, 0.68-0.92] vs 0.99 [95% CI, 0.93-1.05] for controls; P = .01).

Conclusion: In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mitochondrial DNA overreplication, and mitochondrial DNA deletions than typically developing children.

Source: JAMA, Dec 1, 2010;304(22). PMID: 21119085, by Giulivi c, Zhang Y, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, tassone F, Pessah IN. University of California, School of Veterinary Medicine, Department of Molecular Biosciences, Davis, California, USA. [Email: cgiulivi@ucdavis.edu]