1. Mitochondria and Autism
PHM Fall 2015
Coordinator: Dr. Jeffrey Henderson
Instructor: Dr. David Hampson
Mitochondria and Autism
By: Luo Fei Liu, Earl Pacson, Jennifer Tse and Eun Hye Lee
October 13, 2015

2. Autism Neurodevelopmental disorder1 Symptoms emerge at age 2 or 3
impairments in social interactions
communication difficulties
repetitive behaviour
Symptoms emerge at age 2 or 3
Causes?
1American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders American Psychiatric Association. Washington, DC,

3. Mitochondria “Powerhouse of the cell”2
responsible for generating energy
adenosine triphosphate (ATP)
Oxidative phosphorylation occurs
in inner membrane via Electron Transport Chain (ETC)
Has its own genome (mitochondrial DNA)
2Rossignol, D. A., & Frye, R. E. (2012). Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Molecular psychiatry, 17(3),

4. Importance of Mitochondria in Brain Development
Cells of brain require energy2
high density of mitochondria to support energy needs
dysfunction?
reduced neurotransmitter release and low firing rates (developmental delays)
increased oxidative stress and damage from reactive oxygen species
2Rossignol, D. A., & Frye, R. E. (2012). Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Molecular psychiatry, 17(3),

5. Mitochondria Dysfunction and Autism
Autistic patients with classical mitochondrial disease make up a total of 5% of autistic patients2
Co-occurrence suggests a pathogenic relationship
Pathophysiology of mitochondrial disease stems from either genetic anomalies or environmental factors resulting in reduced mitochondrial function
Patients exhibit symptoms common to mitochondrial disease including limb weakness, stroke-like episodes and cardiomyopathy in addition to further cognitive impairments and reduced brain development.
2Rossignol, D. A., & Frye, R. E. (2012). Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Molecular psychiatry, 17(3),

6. Mechanisms Relating Autism and Mitochondrial Disease
Mitochondrial activation of immune system3
Loss of the mitochondria’s regulatory role will lead to immune-mediated mechanisms damaging brain development
Abnormal mitochondrial calcium handling
Upsetting Ca2+ homeostasis can further increase the ratio of excitatory to inhibitory neurotransmitters observed in the autistic population
Oxidative Stress
Inability to prevent damage caused from ROS produced
3Haas, R. H. (2010). Autism and mitochondrial disease. Developmental Disabilities Research Reviews, 16(2), 144–153.

7. Glutathione (GSH & GSSG)
Adapted from lecture slides (2)

8. Biomarkers of Oxidative Stress
Decrease in Reduced Glutathione (GSH)4
Increase in Oxidized Disulfide form (GSSG)
GSH used up to deal with ROS
Exceed GSH reductase capacity to restore GSH levels
Export GSSG to maintain intracellular redox homeostasis
4Palmieri, L., Persico, A.M. (2010). Mitochondrial dysfunction in autism spectrum disorders: Cause or effect? Biochimica et Biophysica Acta 1797:
Inside cell
Outside cell
Adapted from lecture slides (2)

9. Biomarkers of Oxidative Stress
Decrease in cysteine levels4
Oxidized glutathione exported out of cell -> net loss of glutathione
Cysteine depleted to restore GSH levels
Reaction gets pushed forward
Adapted from lecture slides (2)

10. Biomarkers of Oxidative Stress
Decrease in Superoxide Dismutase, Catalase & Glutathione Peroxidase4
Lipid peroxidation
Excessive oxidative stress overload antioxidants
Adapted from lecture slides (2)

11. Suramin
Suramin. Digital image. N.p., n.d. Web.

12. Suramin First created to treat African sleeping sickness
Indirectly blocks a cell’s mitochondrial signals
Mice who received a shot of Suramin showed:5
Restoration of motor coordination
Normal socializing
Less brain abnormalities associated with autism compared to mice who received saltwater injection
Still in research phase as it has potentially serious side effects in humans1
5Hughes, V. (2013, April 15). Drug linked to mitochondria treats mouse model of autism | Spectrum News – Autism Research News. Retrieved October 12, , from

13. Summary
Autism: neurodevelopmental disorder (impairments in social interactions, communication difficulties and repetitive behaviour)
Mitochondrion: generates energy in the form of adenosine triphosphate (ATP) and its dysfunction is associated with symptoms of autism due to high mitochondrial density in brain
Possible Pathogenic relationship between autism and mitochondrial disease
Possible interacting mechanisms include: increased immune activation, abnormal calcium handling and oxidative stress
Decreased GSH levels (reduced form)
Increased GSSG levels (oxidized form)
Decreased cysteine levels
Net loss of glutathione
Decreased SOD, glutathione peroxidase, catalase levels
Lipid peroxidation
Suramin is currently being researched as a drug to treat autism
Suramin blocks purine receptors on the cell surface that are indirectly controlled by mitochondria causing the cell danger response to end

14. References
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders American Psychiatric Association. Washington, DC, Drug Treatment Corrects Autism Symptoms in Mouse Model. (2013, March 13). Retrieved October 12, 2015 from Haas, R. H. (2010). Autism and mitochondrial disease. Developmental Disabilities Research Reviews, 16(2), 144–153. Hughes, V. (2013, April 15). Drug linked to mitochondria treats mouse model of autism | Spectrum News – Autism Research News. Retrieved October 12, 2015, from mouse-model-of-autism/ 100-Year-Old Drug Suramin Under Investigation as Autism Treatment. (2015, June 15). Retrieved October 12, 2015, from treatment/article/ Palmieri, L., Persico, A.M. (2010). Mitochondrial dysfunction in autism spectrum disorders: Cause or effect? Biochimica et Biophysica Acta 1797: Rossignol, D. A., & Frye, R. E. (2012). Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Molecular psychiatry, 17(3),