Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism

Transl Psychiatry. 2013 Sep 3;3(9):e299. doi: 10.1038/tp.2013.68.


Autism is a neurodevelopmental disorder associated with social deficits and behavioral abnormalities. Recent evidence suggests that mitochondrial dysfunction and oxidative stress may contribute to the etiology of autism. This is the first study to compare the activities of mitochondrial electron transport chain (ETC) complexes (I-V) and pyruvate dehydrogenase (PDH), as well as mitochondrial DNA (mtDNA) copy number in the frontal cortex tissues from autistic and age-matched control subjects. The activities of complexes I, V and PDH were most affected in autism (n=14) being significantly reduced by 31%, 36% and 35%, respectively. When 99% confidence interval (CI) of control group was taken as a reference range, impaired activities of complexes I, III and V were observed in 43%, 29% and 43% of autistic subjects, respectively. Reduced activities of all five ETC complexes were observed in 14% of autistic cases, and the activities of multiple complexes were decreased in 29% of autistic subjects. These results suggest that defects in complexes I and III (sites of mitochondrial free radical generation) and complex V (adenosine triphosphate synthase) are more prevalent in autism. PDH activity was also reduced in 57% of autistic subjects. The ratios of mtDNA of three mitochondrial genes ND1, ND4 and Cyt B (that encode for subunits of complexes I and III) to nuclear DNA were significantly increased in autism, suggesting a higher mtDNA copy number in autism. Compared with the 95% CI of the control group, 44% of autistic children showed higher copy numbers of all three mitochondrial genes examined. Furthermore, ND4 and Cyt B deletions were observed in 44% and 33% of autistic children, respectively. This study indicates that autism is associated with mitochondrial dysfunction in the brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Autistic Disorder / enzymology
  • Autistic Disorder / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • DNA Copy Number Variations / genetics*
  • DNA, Mitochondrial / genetics*
  • Electron Transport Chain Complex Proteins / genetics*
  • Electron Transport Chain Complex Proteins / metabolism
  • Female
  • Frontal Lobe / enzymology
  • Frontal Lobe / metabolism*
  • Humans
  • Male
  • Oxidative Stress / genetics
  • Pyruvate Dehydrogenase Complex / genetics*
  • Pyruvate Dehydrogenase Complex / metabolism
  • Young Adult


  • DNA, Mitochondrial
  • Electron Transport Chain Complex Proteins
  • Pyruvate Dehydrogenase Complex