title: Downregulation of the expression of mitochondrial electron transport complex genes in autism brains.
abstract: Mitochondrial dysfunction (MtD) and abnormal brain bioenergetics have been implicated in autism, suggesting possible candidate genes in the electron transport chain (ETC). We compared the expression of 84 ETC genes in the post-mortem brains of autism patients and controls. Brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients (n = 8) and controls (n = 10) were obtained from Autism Tissue Program, USA. Quantitative real-time PCR arrays were used to quantify gene expression. We observed reduced expression of several ETC genes in autism brains compared to controls. Eleven genes of Complex I, five genes each of Complex III and Complex IV, and seven genes of Complex V showed brain region-specific reduced expression in autism. ATP5A1 (Complex V), ATP5G3 (Complex V) and NDUFA5 (Complex I) showed consistently reduced expression in all the brain regions of autism patients. Upon silencing ATP5A1, the expression of mitogen-activated protein kinase 13 (MAPK13), a p38 MAPK responsive to stress stimuli, was upregulated in HEK 293 cells. This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism.
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Taishi
authors.initials: T
authors.lastname: Miyachi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tsujii
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001923:Brain Chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002648:Child; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D003627:Data Interpretation, Statistical; D015536:Down-Regulation; D045222:Electron Transport Chain Complex Proteins / Q000096:biosynthesis / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases; D048292:Mitogen-Activated Protein Kinase 13 / Q000096:biosynthesis / Q000235:genetics; D009245:NADH Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D045222:Electron Transport Chain Complex Proteins; D008565:Membrane Proteins; C508060:NDUFA5 protein, human; D012313:RNA; D009245:NADH Dehydrogenase; D048292:Mitogen-Activated Protein Kinase 13; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; C020439:oligomycin sensitivity-conferring protein