Skip to main content
SpringerLink
Log in

Mitochondrial Dysfunction in Autism

  • Chapter
  • First Online:
Studies on Psychiatric Disorders

Abstract

Autism spectrum disorders (ASDs) are neurodevelopmental disorders that cause behavioral, social, and communication impairments. Several lines of evidence from biochemical, anatomical, and neuroradiographical studies suggest impairment of energy metabolism and mitochondrial dysfunction in ASDs. Mitochondrial electron transport chain (ETC) abnormalities result in reduced production of energy, i.e., adenosine triphosphate (ATP), and enhanced generation of free radicals. Mitochondria also play a central role in maintaining intracellular calcium homeostasis. Both mitochondrial DNA and nuclear DNA (nDNA) encode the subunits of ETC complexes. Any mtDNA mutation or deletion can result in deficiency of ETC complexes and, subsequently, in mitochondrial dysfunction. The brain has a high demand for energy that is provided by mitochondria. Here, we review the evidence about mitochondrial dysfunction in autism, including decreased activities and protein expression levels of ETC complexes, mtDNA or nDNA mutations, oxidative stress, and calcium-signaling abnormalities in autism.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ADP:

Adenosine diphosphate

AGC:

Aspartate/glutamate carrier

ASDs:

Autism spectrum disorders

ATP:

Adenosine triphosphate

ETC:

Electron transport chain

FADH2 :

Dihydrogen flavin adenine dinucleotide

GPx:

Glutathione peroxidase

GSH:

Glutathione

GSSG:

Oxidized glutathione

H2O2 :

Hydrogen peroxide

HEADD:

Hypotonia, intractable epilepsy, autism, and developmental delay

MD:

Mitochondrial disease

MELAS:

Mitochondrial encephalopathy with lactic acidosis and seizures

MMP:

Mitochondrial membrane potential

MRS:

Magnetic resonance spectroscopy

NADH:

Reduced nicotinamide adenine dinucleotide

NO:

Nitric oxide

PDHC:

Pyruvate dehydrogenase complex

ROS:

Reactive oxygen species

SNPs:

Single-nucleotide polymorphisms

SOD:

Superoxide dismutase

TCA:

Tricarboxylic acid

References

  • Abrahams BS, Geschwind DH (2010) Connecting genes to brain in the autism spectrum disorders. Arch Neurol 67:395–399

    PubMed Central  PubMed  Google Scholar 

  • Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D (2011) Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 11:111

    CAS  PubMed Central  PubMed  Google Scholar 

  • Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem 42:1032–1040

    CAS  PubMed  Google Scholar 

  • Ames A (2000) CNS energy metabolism as related to function. Brain Res Brain Res Rev 34:42–68

    CAS  PubMed  Google Scholar 

  • Anderson S, Bankier A, Barrell B, de Bruijn M, Coulson A, Drouin J (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465

    CAS  PubMed  Google Scholar 

  • Bandyopadhyay U, Das D, Banerjee RK (1999) Reactive oxygen species: oxidative damage and pathogenesis. Curr Sci 77:658–666

    CAS  Google Scholar 

  • Barja G (1999) Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr 31:347–366

    CAS  PubMed  Google Scholar 

  • Bertoglio K, Jill James S, Deprey LJ, Brule N, Hendren RL (2010) Pilot study of the effect of methyl B12 treatment on behavioral and biomarker measures in children with autism. J Altern Complement Med 16:555–560

    PubMed  Google Scholar 

  • Bertram R, Gram Pedersen M, Luciani DS, Sherman A (2006) A simplified model for mitochondrial ATP production. J Theor Biol 243:575–586

    CAS  PubMed  Google Scholar 

  • Boekema EJ, Braun HP (2007) Supramolecular structure of the mitochondrial oxidative phosphorylation system. J Biol Chem 282:1–4

    CAS  PubMed  Google Scholar 

  • Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    CAS  PubMed  Google Scholar 

  • Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 57:411–425

    CAS  PubMed  Google Scholar 

  • Chauhan A, Chauhan V (2006) Oxidative stress in autism. Pathophysiology 13:171–181

    CAS  PubMed  Google Scholar 

  • Chauhan V, Chauhan A (2009) Abnormalities in membrane lipids, membrane-associated proteins, and signal transduction in autism. In: Chauhan A, Chauhan V, Brown WT (eds) Autism: oxidative stress, inflammation and immune abnormalities. CRC Press/Taylor and Francis Group, Boca Raton, Florida, pp 177–206

    Google Scholar 

  • Chauhan A, Chauhan V (2012) Brain oxidative stress and mitochondrial abnormalities in autism. In: Fatemi SH, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum 11:777–807

    PubMed Central  PubMed  Google Scholar 

  • Chauhan A, Chauhan V, Brown WT, Cohen I (2004) Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin–the antioxidant proteins. Life Sci 75:2539–2549

    CAS  PubMed  Google Scholar 

  • Chauhan A, Chauhan V, Brown WT (eds) (2009a) Autism: oxidative stress, inflammation and immune abnormalities. CRC Press/Taylor and Francis Group, Boca Raton, Florida

    Google Scholar 

  • Chauhan A, Essa MM, Muthaiyah B, Brown WT, Chauhan V (2009b) Mitochondrial abnormalities in lymphoblasts from autism. J Neurochem 109 (Suppl 1):273

    Google Scholar 

  • Chauhan A, Audhya T, Chauhan V (2011a) Increased DNA oxidation in the cerebellum, frontal cortex of brain in autism. Trans Am Soc Neurochem 42:81

    Google Scholar 

  • Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Brown WT, Chauhan V (2011b) Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem 117:209–220

    CAS  PubMed  Google Scholar 

  • Chauhan A, Audhya T, Chauhan V (2012a) Brain region-specific glutathione redox imbalance in autism. Neurochem Res 37:1681–1689

    CAS  PubMed  Google Scholar 

  • Chauhan A, Gu F, Chauhan V (2012b) Mitochondrial respiratory chain defects in autism and other neurodevelopmental disorders. J Pediatr Biochem 2:213–223

    Google Scholar 

  • Chinnery PF, Schon EA (2003) Mitochondria. J Neurol Neurosurg Psychiatry 74:1188–1199

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chugani DC, Sundram BS, Behen MLML, Moore GJ (1999) Evidence of altered energy metabolism in autistic children. Prog Neuropsychopharmacol Biol Psychiatry 23:635–641

    CAS  PubMed  Google Scholar 

  • Cooper EC, Jan LY (1999) Ion channel genes and human neurological disease: recent progress, prospects, and challenges. Proc Natl Acad Sci U S A 96:4759–4766

    CAS  PubMed Central  PubMed  Google Scholar 

  • Correia C, Coutinho AM, Diogo L, Grazina M, Marques C, Miguel T, Ataide A, Almeida J, Borges L, Oliveira C, Oliveira G, Vicente AM (2006) Brief report: high frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene. J Autism Dev Disord 36:1137–1140

    PubMed  Google Scholar 

  • Cotter D, Guda P, Fahy E, Subramaniam S (2004) MitoProteome: mitochondrial protein sequence database and annotation system. Nucleic Acids Res 32:D463–D467

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dudkina NV, Eubel H, Keegstra W, Boekema EJ, Braun HP (2005) Structure of a mitochondrial supercomplex formed by respiratory-chain complexes I and III. Proc Natl Acad Sci U S A 102:3225–3229

    CAS  PubMed Central  PubMed  Google Scholar 

  • El-Fishawy P, State MW (2010) The genetics of autism: key issues, recent findings, and clinical implications. Psychiatr Clin North Am 33:83–105

    PubMed Central  PubMed  Google Scholar 

  • Essa MM, Muthaitah B, Chauhan V, Brown WT, Chauhan A (2009) Increased oxidative damage in lymphoblasts form autism: enhanced free radical generation coupled with reduced antioxidant status. J Neurochem 108(Suppl 1):73

    Google Scholar 

  • Evans TA, Perry G, Smith MA (2009) Evidence for oxidative damage in the autistic brain. In: Chauhan A, Chauhan V, Brown WT (eds) Autism: oxidative stress, inflammation and immune abnormalities. CRC Press/Taylor and Francis Group, Boca Raton, Florida, pp 35–46

    Google Scholar 

  • Ezugha H, Goldenthal M, Valencia I, Anderson CE, Legido A, Marks H (2010) 5q14.3 deletion manifesting as mitochondrial disease and autism: case report. J Child Neurol 25:1232–1235

    PubMed  Google Scholar 

  • Fattal O, Budur K, Vaughan AJ, Franco K (2006) Review of the literature on major mental disorders in adult patients with mitochondrial disease. Psychosomatics 47:1–7

    PubMed  Google Scholar 

  • Filiano JJ, Goldenthal MJ, Rhodes CH, Marin-Garcia J (2002) Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol 17:435–439

    Google Scholar 

  • Filipek PA, Juranek J, Smith M, Mays LZ, Ramos ER, Bocian M, Masser-Frye D, Laulhere TM, Modahl C, Spence MA, Gargus JJ (2003) Mitochondrial dysfunction in autistic patients with 15q inverted duplication. Ann Neurol 53:801–804

    CAS  PubMed  Google Scholar 

  • Gargus JJ (2009) Genetic calcium signaling abnormalities in the central nervous system: seizures, migraine, and autism. Ann N Y Acad Sci 1151:133–156

    CAS  PubMed  Google Scholar 

  • Gargus JJ, Imtiaz F (2008) Mitochondrial energy-deficient endophenotype in autism. Am J Biochem Biotechnol 4:198–207

    CAS  Google Scholar 

  • Germanò E, Gagliano A, Magazù A, Calarese T, Calabrò ME, Bonsignore M, Tortorella G, Calamoneri F (2006) Neurobiology of autism: study of a sample of autistic children. Minerva Pediatr 58:109–120

    PubMed  Google Scholar 

  • Gillberg C (1998) Chromosomal disorders and autism. J Autism Dev Disord 28:415–425

    CAS  PubMed  Google Scholar 

  • Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN (2010) Mitochondrial dysfunction in autism. JAMA 304:2389–2396

    CAS  PubMed Central  PubMed  Google Scholar 

  • Goldberg WA, Osann K, Filipek PA, Laulhere T, Jarvis K, Modahl C, Flodman P, Spence MA (2003) Language and other regression: assessment and timing. J Autism Dev Disord 33:607–616

    PubMed  Google Scholar 

  • Graf WD, Marin-Garcia J, Gao HG, Pizzo S, Naviaux RK, Markusic D, Barshop BA, Courchesne E, Haas RH (2000) Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. J Child Neurol 15:357–361

    CAS  PubMed  Google Scholar 

  • Guevara-Campos J, Gonzalez-Guevara L, Briones P, Lopez-Gallardo E, Bulan N, Ruiz-Pesini E, Ramnarine D, Montoya J (2010) Autism associated to a deficiency of complexes III and IV of the mitochondrial respiratory chain. Invest Clin 51:423–431

    PubMed  Google Scholar 

  • Haas RH (2010) Autism and mitochondrial disease. Dev Disabil Res Rev 16:144–153

    PubMed  Google Scholar 

  • Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N, Cohen BH (2007) Mitochondrial disease: a practical approach for primary care physicians. Pediatrics 120:1326–1333

    PubMed  Google Scholar 

  • Hansen RL, Ozonoff S, Krakowiak P, Angkustsiri K, Jones C, Deprey LJ, Le DN, Croen LA, Hertz-Picciotto I (2008) Regression in autism: prevalence and associated factors in the CHARGE Study. Ambul Pediatr 8:25–31

    PubMed  Google Scholar 

  • Hemara-Wahanui A, Berjukow S, Hope CI, Dearden PK, Wu SB (2005) A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation. Proc Natl Acad Sci U S A 102:7553–7558

    CAS  PubMed Central  PubMed  Google Scholar 

  • Herbert MR (2010) Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 23:103–110

    PubMed  Google Scholar 

  • Holt R, Monaco AP (2011) Links between genetics and pathophysiology in the autism spectrum disorders. EMBO Mol Med 3:438–450

    CAS  PubMed Central  PubMed  Google Scholar 

  • Holtzman D (2008) Autistic spectrum disorders and mitochondrial encephalopathies. Acta Paediatr 97:859–860

    PubMed  Google Scholar 

  • Hope CI, Sharp DM, Hemara-Wahanui A, Sissingh JI, Lundon P, Mitchell EA, Maw MA, Clover GM (2005) Clinical manifestations of a unique X-linked retinal disorder in a large New Zealand family with a novel mutation in CACNA1F, the gene responsible for CSNB2. Clin Experiment Ophthalmol 33:129–136

    PubMed  Google Scholar 

  • Jacobsen NJ, Lyons I, Hoogendoorn B, Burge S, Kwok PY, O’Donovan MC, Craddock N, Owen MJ (1999) ATP2A2 mutations in Darier’s disease and their relationship to neuropsychiatric phenotypes. Hum Mol Genet 8:1631–1636

    CAS  PubMed  Google Scholar 

  • James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80:1611–1617

    CAS  PubMed  Google Scholar 

  • James SJ, Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, Gaylor DW (2009) Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB J 23:2374–2383

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ji L, Chauhan A, Brown WT, Chauhan V (2009) Increased activities of Na+/K+ −ATPase and Ca2+/Mg2+ −ATPase in the frontal cortex and cerebellum of autistic individuals. Life Sci 85:788–793

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamiya K, Kaneda M, Sugawara T, Mazaki E, Okamura N, Montal M (2004) A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline. J Neurosci 24:2690–2698

    CAS  PubMed  Google Scholar 

  • Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC, Cheon KA, Kim SJ, Kim YK, Lee H, Song DH, Grinker RR (2011) Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry 168:904–912

    PubMed  Google Scholar 

  • Laszlo A, Horvath E, Eck E, Fekete M (1994) Serum serotonin, lactate and pyruvate levels in infantile autistic children. Clin Chim Acta 229:205–207

    CAS  PubMed  Google Scholar 

  • Laumonnier F, Roger S, Guérin P, Molinari F, M’rad R, Cahard D (2006) Association of a functional deficit of the BKCa channel, a synaptic regulator of neuronal excitability, with autism and mental retardation. Am J Psychiatry 163:1622–1629

    PubMed  Google Scholar 

  • Lenaz G (2001) The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 52:159–164

    CAS  PubMed  Google Scholar 

  • Li Z, Okamoto K, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119:873–887

    CAS  PubMed  Google Scholar 

  • Lombard J (1998) Autism: a mitochondrial disorder? Med Hypotheses 50:497–500

    CAS  PubMed  Google Scholar 

  • López-Hurtado E, Prieto JJ (2008) A microscopic study of language-related cortex in autism. Am J Biochem Biotechnol 4:130–145

    Google Scholar 

  • Lord C, Cook EH, Leventhal BL, Amaral DG (2000) Autism spectrum disorders. Neuron 28:355–363

    CAS  PubMed  Google Scholar 

  • Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Jinde S, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N (2011) The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism. Acta Psychiatr Scand 123:118–124

    CAS  PubMed  Google Scholar 

  • Mattson MP, Liu D (2002) Energetics and oxidative stress in synaptic plasticity and neurodegenerative disorders. Neuromolecular Med 2:215–231

    CAS  PubMed  Google Scholar 

  • Meguid NA, Dardir AA, Abdel-Raouf ER, Hashish A (2011) Evaluation of oxidative stress in autism: defective antioxidant enzymes and increased lipid peroxidation. Biol Trace Elem Res 143:58–65

    CAS  PubMed  Google Scholar 

  • Miles JH (2011) Autism spectrum disorders–a genetics review. Genet Med 13:278–294

    PubMed  Google Scholar 

  • Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC (2005) Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids 73:379–384

    CAS  PubMed  Google Scholar 

  • Minshew NJ, Goldstein G, Dombrowski SM, Panchalingam K, Pettegrew JW (1993) A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes. Biol Psychiatry 33:762–773

    CAS  PubMed  Google Scholar 

  • Moreno H, Borjas L, Arrieta A, Sáez L, Prassad A, Estévez J, Bonilla E (1992) Clinical heterogeneity of the autistic syndrome: a study of 60 families. Invest Clin 33:13–31

    CAS  PubMed  Google Scholar 

  • Mostafa GA, El-Gamal HA, El-Wakkad ASE, El-Shorbagy OE, Hamza MM (2005) Polyunsaturated fatty acids, carnitine and lactate as biological markers of brain energy in autistic children. Int J Child Neuropsychiatry 2:179–188

    Google Scholar 

  • Mostafa GA, El-Hadidi ES, Hewedi DH, Abdou MM (2010) Oxidative stress in Egyptian children with autism: relation to autoimmunity. J Neuroimmunol 219:114–118

    CAS  PubMed  Google Scholar 

  • Muller FL, Liu Y, Van Remmen H (2004) Complex III releases superoxide to both sides of the inner mitochondrial membrane. J Biol Chem 279:49064–49073

    CAS  PubMed  Google Scholar 

  • Muthaiyah B, Essa MM, Chauhan V, Brown WT, Wegiel J, Chauhan A (2009) Increased lipid peroxidation in cerebellum and temporal cortex of brain in autism. J Neurochem 108(Suppl 1):73

    Google Scholar 

  • Napolioni V, Persico AM, Porcelli V, Palmieri L (2011) The mitochondrial aspartate/glutamate carrier AGC1 and calcium homeostasis: physiological links and abnormalities in autism. Mol Neurobiol 44:83–92

    CAS  PubMed  Google Scholar 

  • Oliveira G, Diogo L, Grazina M, Garcia P, Ataide A, Marques C, Miguel T, Borges L, Vicente AM, Oliveira CR (2005) Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol 47:185–189

    CAS  PubMed  Google Scholar 

  • Orth M, Schapira AH (2011) Mitochondria and degenerative disorders. Am J Med Genet 106:27–36

    Google Scholar 

  • Ozonoff S, Williams BJ, Landa R (2005) Parental report of the early development of children with regressive autism: the delays-plus-regression phenotype. Autism 9:461–486

    PubMed  Google Scholar 

  • Palmieri L, Persico AM (2010) Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochim Biophys Acta 1797:1130–1137

    CAS  PubMed  Google Scholar 

  • Palmieri L, Papaleo V, Porcelli V, Scarcia P, Gaita L (2010) Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1. Mol Psychiatry 15:38–52

    CAS  PubMed  Google Scholar 

  • Pastural E, Ritchie S, Lu Y, Jin W, Kavianpour A, Khine Su-Myat K, Heath D, Wood P, Fisk M, Goodenowe D (2009) Novel plasma phospholipid biomarkers of autism: mitochondrial dysfunction as a putative causative mechanism. Prostaglandins Leukot Essent Fatty Acids 81:253–264

    CAS  PubMed  Google Scholar 

  • Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83:117–161

    CAS  PubMed  Google Scholar 

  • Poling JS, Frye RE, Shoffner J, Zimmerman AW (2006) Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol 21:170–172

    PubMed Central  PubMed  Google Scholar 

  • Polster BM, Fiskum G (2004) Mitochondrial mechanisms of neural cell apoptosis. J Neurochem 90:1281–1289

    CAS  PubMed  Google Scholar 

  • Pons R, Andreu AL, Checcarelli N, Vila MR, Engelstad K, Sue CM, Shungu D, Haggerty R, de Vivo DC, DiMauro S (2004) Mitochondrial DNA abnormalities and autistic spectrum disorders. J Pediatr 144:81–85

    CAS  PubMed  Google Scholar 

  • Ramoz N, Reichert JG, Smith CJ, Silverman JM, Bespalova IN, Davis KL, Buxbaum JD (2004) Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. Am J Psychiatry 161:662–669

    PubMed  Google Scholar 

  • Robin ED, Wong R (1988) Mitochondrial DNA molecules and virtual number of mitochondria per cell in mammalian cells. J Cell Physiol 136:507–513

    CAS  PubMed  Google Scholar 

  • Rossignol DA, Bradstreet JJ (2008) Evidence of mitochondrial dysfunction in autism and implications for treatment. Am J Biochem Biotechnol 4:208–217

    CAS  Google Scholar 

  • Rossignol DA, Frye RE (2012) Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 17:290–314

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sajdel-Sulkowska EM, Xu M, McGinnis W, Koibuchi N (2011) Brain region-specific changes in oxidative stress and neurotrophin levels in autism spectrum disorders (ASD). Cerebellum 10:43–48

    CAS  PubMed  Google Scholar 

  • Scaglia F, Zhang S, Tan Z, Fouladi N, Schmitt E, Wong L-J (2009) Prevalence of autism spectrum disorders in subjects with definite diagnosis of mitochondrial cytopathies. In: Proceedings of the American Society of Human Genetics 59th annual meeting, Honolulu, Hawaii

    Google Scholar 

  • Schroer RJ, Phelan MC, Michaelis RC, Crawford EC, Skinner SA, Cuccaro M, Simensen RJ, Bishop J, Skinner C, Fender D, Stevenson RE (1998) Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 76:327–336

    CAS  PubMed  Google Scholar 

  • Segurado R, Conroy J, Meally E, Fitzgerald M, Gill M, Gallagher L (2005) Confirmation of association between autism and the mitochondrial aspartate/glutamate carrier SLC25A12 gene on chromosome 2q31. Am J Psychiatry 162:2182–2184

    PubMed  Google Scholar 

  • Shadel GS (2008) Expression and maintenance of mitochondrial DNA: new insights into human disease pathology. Am J Pathol 172:1445–1456

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shadel GS, Pan Y (2009) Multi-faceted regulation of mitochondria by TOR. Cell Cycle 8:2143

    CAS  PubMed  Google Scholar 

  • Shay JW, Pierce DJ, Werbin H (1990) Mitochondrial DNA copy number is proportional to total cell DNA under a variety of growth conditions. J Biol Chem 265:14802–14807

    CAS  PubMed  Google Scholar 

  • Shoffner J, Hyams L, Langley GN, Cossette S, Mylacraine L, Dale J, Ollis L (2010) Fever plus mitochondrial disease could be risk factors for autistic regression. J Child Neurol 25:429–434

    PubMed  Google Scholar 

  • Skladal D, Halliday J, Thorburn DR (2003) Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 126:1905–1912

    PubMed  Google Scholar 

  • Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C (2004) Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119:19–31

    CAS  PubMed  Google Scholar 

  • Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB (2005) Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A 102:8089–8096

    CAS  PubMed Central  PubMed  Google Scholar 

  • Splawski I, Yoo DS, Stotz SC, Cherry A, Clapham DE, Keating MT (2006) CACNA1H mutations in autism spectrum disorders. J Biol Chem 281:22085–22091

    CAS  PubMed  Google Scholar 

  • Stefanatos GA (2008) Regression in autistic spectrum disorders. Neuropsychol Rev 18:305–319

    PubMed  Google Scholar 

  • Sugioka K, Nakano M, Totsune-Nakano H, Minakami H, Tero-Kubota S, Ikegami Y (1988) Mechanism of O2-generation in reduction and oxidation cycle of ubiquinones in a model of mitochondrial electron transport systems. Biochim Biophys Acta 936:377–385

    CAS  PubMed  Google Scholar 

  • Szewczyk A, Wojtczak L (2002) Mitochondria as a pharmacological target. Pharmacol Rev 54:101–127

    CAS  PubMed  Google Scholar 

  • Taurines R, Thome J, Duvigneau JC, Forbes-Robertson S, Yang L, Klampfl K, Romanos J, Muller S, Gerlach M, Mehler-Wex C (2010) Expression analyses of the mitochondrial complex I 75-kDa subunit in early onset schizophrenia and autism spectrum disorder: increased levels as a potential biomarker for early onset schizophrenia. Eur Child Adolesc Psychiatry 19:441–448

    PubMed  Google Scholar 

  • Tsao CY, Mendell JR (2007) Autistic disorder in 2 children with mitochondrial disorders. J Child Neurol 22:1121–1123

    PubMed  Google Scholar 

  • Weiss LA, Escayg A, Kearney JA, Trudeau M, MacDonald BT, Mori M, Reichert JG, Buxbaum JD, Meisler MH (2003) Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol Psychiatry 8:186–194

    CAS  PubMed  Google Scholar 

  • Weissman JR, Kelley RI, Bauman ML, Cohen BH, Murray KF, Mitchell RL, Kern RL, Natowicz MR (2008) Mitochondrial disease in autism spectrum disorder patients: a cohort analysis. PLoS One 3:e3815

    PubMed Central  PubMed  Google Scholar 

  • Wingate M, Kirby RS, Pettygrove S, Cunniff C (2014) Prevalence of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ 63:1–21

    Google Scholar 

  • Zoroglu SS, Armutcu F, Ozen S, Gurel A, Sivasli E, Yetkin O, Meram I (2004) Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci 254:143–147

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by funds from the New York State Office for People With Developmental Disabilities, the Department of Defense Autism Spectrum Disorders Research Program AS073224P2, the Autism Research Institute, and the Autism Collaboration.

Author information

Authors and Affiliations

  1. Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA

    Abha Chauhan Ph.D., Feng Gu Ph.D. & Ved Chauhan Ph.D.

Authors
  1. Abha Chauhan Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng Gu Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ved Chauhan Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abha Chauhan Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Biological Psychiatry of the Chair of Experimental and Clinical Physiology, Medical University of Lodz, Lodz, Poland

    Anna Dietrich-Muszalska

  2. Department of Neurochemistry, New York State Institute for Basic Research, Staten Island, New York, USA

    Ved Chauhan

  3. Departments of Psychiatry and Physiology & Biophysics, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Sylvain Grignon

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chauhan, A., Gu, F., Chauhan, V. (2015). Mitochondrial Dysfunction in Autism. In: Dietrich-Muszalska, A., Chauhan, V., Grignon, S. (eds) Studies on Psychiatric Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0440-2_17

Download citation

Publish with us

Policies and ethics

Search

Navigation