title: Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study.
abstract: Autism spectrum disorder (ASD) is associated with physiological abnormalities, including abnormal redox and mitochondrial metabolism. Lymphoblastoid cell lines (LCLs) from some children with ASD exhibit increased oxidative stress, decreased glutathione redox capacity, and highly active mitochondria with increased vulnerability to reactive oxygen species (ROS). Because unaffected siblings (Sibs) of individuals with ASD share some redox abnormalities, we sought to determine whether LCLs from Sibs share ASD-associated mitochondrial abnormalities. We evaluated mitochondrial bioenergetics in 10 sets of LCLs from children with ASD, Sibs, and unrelated/unaffected controls (Cons) after acute increases in ROS. Additionally, intracellular glutathione and uncoupling protein 2 (UCP2) gene expressions were quantified. Compared to Sib LCLs, ASD LCLs exhibited significantly higher ATP-linked respiration, higher maximal and reserve respiratory capacity, and greater glycolysis and glycolytic reserve. ASD LCLs exhibited a significantly greater change in these parameters, with acute increases in ROS compared to both Sib and Con LCLs. Compared to Con, both ASD and Sib LCLs exhibited significantly higher proton leak respiration. Consistent with this, intracellular glutathione redox capacity was decreased andUCP2gene expression was increased in both ASD and Sib compared to Con LCLs. These data indicate that mitochondrial respiratory function, not abnormal redox homeostasis, distinguishes ASD from unaffected LCLs.-Rose, S., Bennuri, S. C., Wynne, R., Melnyk, S., James, S. J., Frye, R. E. Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study.
authors.affiliation: Arkansas Children's Research Institute, Little Rock, Arkansas, USA; and srose@uams.edu.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Rose
authors.affiliation: Arkansas Children's Research Institute, Little Rock, Arkansas, USA; and.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Sirish C
authors.initials: SC
authors.lastname: Bennuri
authors.affiliation: Arkansas Children's Research Institute, Little Rock, Arkansas, USA; and.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wynne
authors.affiliation: Arkansas Children's Research Institute, Little Rock, Arkansas, USA; and.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Stepan
authors.initials: S
authors.lastname: Melnyk
authors.affiliation: Arkansas Children's Research Institute, Little Rock, Arkansas, USA; and.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: S Jill
authors.initials: SJ
authors.lastname: James
authors.affiliation: Arkansas Children's Research Institute, Little Rock, Arkansas, USA; and.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Frye
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D035781:Siblings; D000071246:Uncoupling Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D000255:Adenosine Triphosphate; D005978:Glutathione
keywords: UCP2; autistic disorder; bioenergetics; glutathione; oxidative stress