Classically, mitochondrial dysfunction was felt to be relatively rare, and it was usually investigated in cases of chronic fatigue, unexplained muscle weakness, that sort of thing - we medical types are a literal lot. "Goodness, you have no energy? Maybe we should see if your cells can make energy."
However, my readers know that that pile of gelatin quivering between your ears is one of the most energy hungry parts of the human body. It is 5% of our body weight, but comprises 20% of our metabolism. Therefore, any genetic predisposition to dysfunctional mitochondria may show up was a brain problem.
Earlier this week, this article was published in JAMA, "Mitochondrial dysfunction in autism." This is the first study to examine the function of mitochondria in a well-defined population of children with autism, which is a disorder that strikes in infancy to early childhood and can result in poor social skills, developmental delay, and stereotypical repetitive movements among other symptoms. It was a small study, 10 children diagnosed with full spectrum autistic disorder and 10 controls, but they examined everything soup to nuts, as it were.
The children and their cells were examined for problems with mitochondrial DNA, the actual energy-generating capacity of their actual mitochondria (lymphocytes* were put on ice and immediately taken to a lab to measure the respiration!), and for signs of leftover metabolic garbage hanging around. The results were pretty remarkable.
Cell respiration (mitochondrial capacity to take glucose (or ketones!) and oxygen and turn it into energy) can be measured by the amount of input of fuel and output of the byproducts of respiration. I'm not the most mechanical of people, but I imagine measuring cell respiration has the automotive equivalent of measuring horsepower. Some of us have Ferraris, others Ford Festivas, and most will be somewhere in between. The autistic kids had lower average NADH oxidase activity - their average was 4.4 (95% CI, 2.8-6) as opposed to 12 (95% CI, 8-16) in the control kids, and the majority of the autistic kids had levels that were below the range of the control kids. The mitochondria of the autistic kids seemed to putter along, compared to the more zippy mitochondria of the control kids.
Now let's look at some metabolic byproducts of slow or inefficient cell respiration. Higher pyruvate levels were found in the autistic kids (pyruvate levels should be relatively low if your mitochondria are efficiently processing oxygen and glucose) than in controls (0.23 vs 0.08), and 8 out of the 10 autistic kids had pyruvate levels higher than any of the controls. This finding matched the decreased amount of pyruvate dehydrogenase activity found in the autistic kids. Levels of hydrogen peroxide were also higher in autistic kids.
At a genetic level, the kids with autism had a lot more copies of mitochondrial DNA in their cells. (Our mitochondria are probably evolved from energy-producing bacteria that another ingenious and cheeky cell gobbled up long, long ago to create its own internal power plant. Therefore our mitochondria, within our big old animal cells, have their own DNA called "mitochondrial DNA." This mDNA (also sometimes called mtDNA) is inherited from our mother, and her mother, and her mother etc. etc. back to that first precocious gobbling cell, as we get all our cell organelles from our mother's egg, and only a bit of good old human DNA from Dad.). An average human cell mitochondria has 2-10 copies of its DNA hanging around. 5 of the autistic kids had more mDNA than expected. 2 of the autistic kids also had deletions of certain areas of their mitochondrial DNA.
So what does all this data mean? It was felt, all told, that the autistic children had cells that were in a state of chronic oxidative stress. This would explain not only the respiration issues, but also the higher copies of mitochondrial DNA, made either due to errors from free radical damage, or to compensate for the inefficient mitochondria. But don't jump to conclusions. We don't know if mitochondrial dysfunction is the cause of autism, or one of the myriad effects. Maybe the kids were born with Ferraris, but adulterants in the fuel causes it to run like a Ford Festiva. It also make sense, as we know the brain needs efficient mitochondria motoring along to keep all those ion gradients that power thinking online, that inherited defects in mitochondria could leave one more vulnerable to developmental insults and problems as the brain forms.
This finding could relate to modern diets and habits in all sorts of ways. It occurs to me that one stand-out epidemiologic link to increased rates of autism is in kids whose moms had gestational diabetes, so presumably higher glucose, insulin, and other neuronal hardships for the developing baby. We also know that ketosis helps mitochondrial efficiency and promotes neurogenesis and neuronal repair - vitamin D also has a role in promoting neuronal repair. And inflammation in general would require mitochondria to be in tip top shape to keep up with the metabolic requirements and clean-up.
I love it when a little more information comes along in real time to add a piece to the puzzle.
*lymphocytes are cells of the immune systems and easily sampled from a simple blood test, compared to painful muscle biopsies or scary brain biopsies. Since lymphocytes use equal amounts glycolysis and oxidative phosphorylation to make energy, it was felt they would be a fair tissue to use to measure oxidative capacity of the cells of the autistic children versus the control children.
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