Mitochondrial Dysfunction in Autism

Abnormalities in Mitochondrial Function in Autism Spectrum Disorder

Abnormalities in mitochondrial function appear to affect a significant number of children with autism spectrum disorder (ASD) but the nature of these abnormalities is poorly understood. Through critical literature reviews, clinical research and basic research, my team and I have investigated the nature of mitochondrial abnormalities in ASD. Our recent research suggests the nature of mitochondrial dysfunction in ASD is distinct from other forms of mitochondrial disease in its metabolic nature and with respect to molecular signaling pathways. We have developed a model of mitochondrial dysfunction related to ASD based on cell lines to allow us to study it in the laboratory in detail.

 

Clinical Studies on Mitochondrial Function in Autism

Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder.

Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE.
Mol Diagn Ther. 2018 Oct;22(5):571-593.

Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.

Rossignol, D., Frye, R.E. Molecular Psychiatry, 2012; 17(3):290-314. DOI: 10.1038/mp.2010.136. PMID: 21263444

Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders.

Frye, R.E., Rossignol, D.A. Pediatr Res. 2011; 69(5 Pt 2):41R-7R.

Redox Metabolism Abnormalities in Autistic Children Associated with Mitochondrial Disease

Frye, R.E., DeLaTorre, R. Taylor, H. Slattery, J., Melnyk, S. James, S.J.Translational Psychiatry, 2013 3:e273. DOI: 10.1038/tp.2013.51. PMID: 23778583

Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study.

Rose, S., Bennuri, S.C., Murray, K.F., Buie, T., Winter, H., Frye, R.E. PLoS One. 2017 Oct 13;12(10):e0186377.

Bioenergetic variation is related to autism symptomatology.

Delhey, L., Kilinc, E.N., Yin, L., Slattery, J., Tippett, M., Wynne, R., Rose, S., Kahler, S., 
Damle, S., Legido, A., Goldenthal, M.J., Frye, R.E.. Metab Brain Dis. 2017; 32(6):2021-2031.

Novel biomarkers of metabolic dysfunction is autism spectrum disorder: potential for biological diagnostic markers.

Khemakhem, A.M., Frye, R.E., El-Ansary, A., Al-Ayadhi, L., Bacha, A.B. Metab Brain Dis. 2017; 32(6):1983-1997.

The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder.

Delhey, L.M., Nur Kilinc, E., Yin, L., Slattery, J.C., Tippett, M.L., Rose, S., Bennuri, S.C.,
Kahler, S.G., Damle, S., Legido, A., Goldenthal, M.J., Frye, R.E.
J Clin Med. 2017; 6(2). pii: E18.

Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome.

Frye, R.E., Rose, S., Slattery, J., MacFabe, D.F. Microb Ecol Health Dis. 2015; 26:27458.

Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder.

Frye RE. Epilepsy Behav. 2015; 47:147-57.

Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism.

Rossignol, D.A., Frye, R.E. Front
Physiol. 2014; 22;5:150.

Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder.

Frye, R.E., Melnyk, S., Macfabe, D.F. Transl Psychiatry. 2013; 3:e220.

A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures.

Rossignol, D.A., Frye, R.E.
Mol Psychiatry. 2012; 17(4):389-401. 

Substantial problems with measuring brain mitochondrial
dysfunction in autism spectrum disorder using magnetic resonance spectroscopy

Rossignol, D.A., Frye, R.E. J 
Autism Dev Disord. 2012; 42(4):640-2.

 

Case Studies of mitochondrial dysfunction in children with autism spectrum disorder

Developmental regression and mitochondrial dysfunction in a child with autism.

Poling, J.S., Frye, R.E., Shoffner, J., Zimmerman, A.W. J Child Neurol. 2006; 21(2):170-2.

Mitochondrial disease in 22q13 duplication syndrome.

Frye RE. J Child Neurol. 
2012; 27(7):942-9.

Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome.

Frye, R.E., Cox, D., Slattery, J., Tippett, M., Kahler, S., Granpeesheh, D., Damle, S.,
Legido, A., Goldenthal, M.J. Sci Rep. 2016 Jan 29;6:19544.

Autistic Siblings with Novel Mutations in Two Different Genes: Insight forGenetic Workups of Autistic Siblings and Connection to Mitochondrial Dysfunction.

Burger, B.J., Rose, S., Bennuri, S.C., Gill, P.S., Tippett, M.L., Delhey, L., Melnyk, S., Frye,
R.E.. Front Pediatr. 2017; 5:219.

 

Cellular Models of Mitochondrial Dysfunction in Autism

Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study.

Rose, S., Bennuri, S.C., Wynne, R., Melnyk, S., James, S.J., Frye, R.E. FASEB J. 2017; 31(3):904-909.

Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines.

Rose, S., Frye, R.E., Slattery, J., Wynne, R., Tippett, M., Melnyk, S., James, S.J. Transl Psychiatry. 2014; 4:e377.

Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort.

Rose, S., Frye, R.E., Slattery, J., Wynne, R., Tippett, M., Pavliv, O., Melnyk, S., James, S.J.
PLoS One. 2014; 9(1):e85436

 

Toxicants Modulate mitochondrial function in Cellular models of
autism spectrum disorder

Oxidative Stress Challenge Uncovers Trichloroacetaldehyde
Hydrate-Induced Mitoplasticity in Autistic and Control Lymphoblastoid Cell Lines.

Frye, R.E., Rose, S., Wynne, R., Bennuri, S.C., Blossom, S., Gilbert, K.M., Heilbrun, L.,
Palmer, R.F. Sci Rep. 2017; 7(1):4478.

Increased susceptibility to ethylmercury-induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines.

Rose, S., Wynne, R., Frye, R.E., Melnyk, S., James, S.J. J Toxicol. 2015; 2015:573701.

 

enteric short chain fatty acids modulate mitochondrial function in in cell line model of autism spectrum disorder

Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism.

Rose, S., Bennuri, S..C, Davis, J.E., Wynne, R., Slattery, J.C., Tippett, M., Delhey, L.,
Melnyk, S., Kahler, S.G., MacFabe, D.F., Frye, R.E.. Transl
Psychiatry. 2018; 8(1):42.

Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines.

Frye, R.E., Rose, S., Chacko. J, Wynne, R., Bennuri, S.C., Slattery, J.C., Tippett, M., Delhey, L,. Melnyk, S., Kahler, S.G., MacFabe, D.F. Transl
Psychiatry. 2016; 6(10):e927.