title: Deficits in bioenergetics and impaired immune response in granulocytes from children with autism.
abstract: Despite the emerging role of mitochondria in immunity, a link between bioenergetics and the immune response in autism has not been explored. Mitochondrial outcomes and phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst were evaluated in granulocytes from age-, race-, and gender-matched children with autism with severity scores of ≥7 (n = 10) and in typically developing (TD) children (n = 10). The oxidative phosphorylation capacity of granulocytes was 3-fold lower in children with autism than in TD children, with multiple deficits encompassing ≥1 Complexes. Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions. Mitochondrial dysfunction in children with autism was accompanied by a lower (26% of TD children) oxidative burst by PMA-stimulated reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and by a lower gene expression (45% of TD children's mean values) of the nuclear factor erythroid 2-related factor 2 transcription factor involved in the antioxidant response. Given that the majority of granulocytes of children with autism exhibited defects in oxidative phosphorylation, immune response, and antioxidant defense, our results support the concept that immunity and response to oxidative stress may be regulated by basic mitochondrial functions as part of an integrated metabolic network.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Napoli
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wong
authors.affiliation: Department of Public Health Sciences, School of Medicine, and Medical Investigations of Neurodevelopmental Disorders (M. I. N. D.) Institute, University of California, Davis, Davis California.
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, Medical Investigations of Neurodevelopmental Disorders (M. I. N. D.) Institute, University of California, Davis, Davis California cgiulivi@ucdavis.edu.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Giulivi
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000276:immunology*; D004734:Energy Metabolism / Q000502:physiology*; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides
keywords: NADPH oxidase; NFE2L2; Nrf2; autism; bioenergetics; immune response; mitochondria; oxidative stress
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