Autism & Mitochondrial Dysfunction

1. Autism & Mitochondrial Dysfunction Kristen Waggoner & Jessica Harrison

2. Relevance • According to the U.S. Centers for Disease Control and Prevention, there are approximately 1 out of each 110 children in American diagnosed on the autism spectrum. • This is a 600% increase in just the last 20 years. It is the fastest-growing serious developmental disability in America. • It is 3 to 4 times more common in males than females. • There are around 3 million people with ASD in the U.S. alone and tens of millions around the globe. • More children will be diagnosed this year than with childhood cancer, pediatric AIDS, and juvenile diabetes combined.

3. What is Autism? • Autism spectrum disorder (ASD) is a general term for a group of complex disorders of brain development. • Can be seen in varying degrees and in varying conditions, like Asperger’s, Rett Syndrome, or autistic disorder. • Characterized by: • Difficulties in social interaction • Delayed verbal and nonverbal communication • Repetitive behaviors • It is sometimes, but not always, associated with: • Poor motor coordination • Intellectual disability • Trouble paying attention and focusing • Health issues, like sleep disorders and gastrointestinal problems

4. What is Autism, cont. • Diagnosis is based only on observation of behavior. • However, behavior is not the only thing affected. The 3 major systems that are affected are: • Neurological • Immunologic • Gastrointestinal • There are varying theories for the causes of autism. • One of these theories is mitochondrial dysfunction.

5. Mitochondria • The cell’s power producers. • Take food energy and convert it to ATP, which the cell uses as fuel. • Can be anywhere from a few to several thousand, depending on the cell type. • Shaped like a tube or are oblong and bound by double membranes, which divide them into two parts (the intermembrane space and mitochondrial matrix). • Can divide and grow to produce more. • Have their own DNA and ribosomes.

6. http://www.youtube.com/watch?v=EZgSv-396vQ

7. What is Mitochondrial Disease? • Mitochondria – organelles in the cell that are often referred to as the “powerhouses” because they are responsible for taking food energy and converting it into the ATP that powers cell functions. • When the mitochondria are dysfunctional, they can cause a group of disorders called mitochondrial disease. • Often caused by genetics or mutations of the mitochondrial DNA. • Includes varied symptoms, depending distribution of the dysfunctional mitochondria.

8. How does this relate to Autism? • Study in The Journal of the American Medical Association by University of California, “Mitochondrial Dysfunction in Autism” found an acquired loss of the ability to produce energy in cells, damage to mitochondria, and increase in oxidative stress, all of which adds up to mitochondrial disease. • It is thought that the type of mitochondrial dysfunction that leads to autism isn’t genetic, it’s epigentic.

9. Epigenetics and Autism • Epigentics – • If your genome (genes) is compared to a computer’s hardware, the epigenome is the software that tells it how to function. • Changing of the genome is done by DNA methylation (when 1 carbon atom attaches to 3 hydrogen atoms), which can turn the gene on, off, or make it “louder” or “dampen” it, depending on where it attaches on the gene. • If autism was just genetic, there should always be 1 out of 100 people with it. • A drug administered to a fly affects the next 13 generations. With this in mind, the claims of vaccines preceding the onset of autism might be a clue. • It is thought that the drugs, among other environmental factors, might trigger the change in expression of genes that leads to autism.

11. Environmental Aspects • In one study by James et al., children with autism are more likely to be affected by environmental toxins. • For example, diesel exhaust exhibits a high correlation with mitochondrial dysfunction. • Other examples of toxins that may contribute to this trait are mercury, lead, and pesticides.

12. Modes of Communication • Retrograde Communication • Mitochondrial dysfunction is responsible for a response of organelles called “retrograde communication” • Many studies have shown that “retrograde communication” serves as a stress response mechanism to balnce out metabolic activity in mitochondria. • One example in this study is yeast.

13. Modes of Communication, cont. • Mitochondrial Trafficking • Mitochondrial trafficking is for maintaining neuronal and mitochondrial health. • The termination of movement may lead to mitochondrial dysfunctions. • Research done on autistic children showed far less energy pathways in the mitochondria than the mitochondria of children without autism. • About 80 percent of autistic children have lower mitochondrial enzyme function. • Showing the high correlation between mitochondrial dysfunction and autism.

14. Conclusion/Summary • Based on our findings, we can conclude that there is a high correlation between mitochondrial dysfunction and Autism. • Recent studies on children with autism have shown slowed energy transportation at synapses which cause mitochondrial dysfunction. • Environmental influences such as pesticides have also shown to cause a dysfunction in the mitochondrial DNA.

15. What does this mean for Autism? • There are many unanswered questions about ASD. • Is Autism a genetic disorder based in the brain or a biological condition? • If it is a biological condition, is it reversible or curable? • How could we prevent it and stop the rapid growth in the rate of individuals diagnosed with Autism? • Mitochondrial dysfunction is a new discovery in relation to autism. Much more research needs to be done, but this new finding gives hope that Autism is acquired (epigenetic) and biological and can one day in the future be reversed. • If researchers can find a way to produce more energy in damaged mitochondria, the chain of events that is now looked to as a cause of autism could be stopped.

16. Works Cited • Bailey, Regina. "What Are Mitochondria?" Biology. 16 Aug. 2008. Web. 14 Nov. 2011. <http://biology.about.com/b/2008/08/16/what-are-mitochondria.htm>. • Chang, Diane. (2005) Mitochondrial Trafficking in Healthy and Injured Neurons. University of Pittsburg Dissertation. http://etd.library.pitt.edu/ETD/available/etd-12132005- 112751/unrestricted/Chang-DTW-Dec05.pdf • Heckenlively, Kent. "TIME Magazine on Epigenetics and Autism." AGE OF AUTISM. Stem Cell Institute, 19 Jan. 2010. Web. 14 Nov. 2011. <http://www.ageofautism.com/2010/01/time-magazine-on-epigenetics-and- autism.html>. • Lord, C., S. Risi, L. Lambrecht, E. H. Cook, B. L. Leventhal, P. C. DiLavore, A. Pickles, and M. Rutter. "The Autism Diagnostic Observation Schedule-generic: a Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism." Journal of Autism and Developmental Disorder 30.3 (2000): 205-23. Web. 14 Nov. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/11055457>. • Rossignol, D. A., and R. E. Frye. "Miotochondrial Dysfunction in Autism Spectrum Disorders: a Systematic Review and Meta-analysis." Molecular Psychiatry (2011). 25 Jan. 2011. Web. 14 Nov. 2011. <http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2010136a.html#bib35>. • Ruiz Villarreal, Mariana. Mitochondrion. Digital image. Wikimedia Commons. Web. 14 Nov. 2011. <http://biology.about.com/od/cellanatomy/ss/mitochondria.htm>. • Parikh V. S., M. M. Morgan, R. Scott, L. S. Clements, and R. A. Butow (1987) The mitochondrial genotype can influence nuclear gene expression in yeast. Science, 235, 576–580. • Wang H. and R. Morais (1997) Up-regulation of nuclear genes in response to inhibition of mitochondrial DNA expression in chicken cells. BiochimBiophysActa, 1352, 325–334.