Mitochondrial Dysfunction/Low Muscle Tone

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This is not a comprehensive list, simply some articles I have found along the way.

“Mitochondrial Dysfunction is a Primary Event in Glutamate Neurotoxcity”

“Glutamate becomes an excitotoxin when it is in excess; meaning it overstimulates brain cells and nerves and results in neurological inflammation and cell death” (

“These results suggest that glutamate targets the mitochondria and selenium supplementation within physiological concentration is capable of preventing the detrimental effects of glutamate on the mitochondria”

“Two biomarkers of this glutatmate excitotoxicity are mitochondrial dysfunction involving 1) viral exposures which damages the mitochondrial membrane resulting in formation of swellings (dendritic beading) along the nerve dendrites and 2) the formation of lipid rafts, ceramides within the cells impairing mebrane function.  The authors assert that the appearance of dendritic beading is indicative of a damaged mitochondrial membrane, made up of fatty acids called cardiolipin, after exposure to a virus.  They have also observed that calcium disregulation is also an accompaniment to mitochondrial dysfunction, leading inevitably to oxidative stress.”

“Excitotoxins such as glutamate and aspartate cause the neuron to fire without rest. Stimulating a neuron beyond its ability to recover produces inflammation and possible cell death. Even one occasion of inflammation in the central nervous system is significant. Animal studies have illustrated that a single injection of an inflammatory stimulator into the body was sufficient to cause this reaction.”(

Glutamate-induced cytotoxicity is partially mediated by enhanced oxidative stress. The objectives of the present study are to determine the effects of glutamate on mitochondrial membrane potential, oxygen consumption, mitochondrial dynamics and autophagy regulating factors and to explore the protective effects of selenium against glutamate cytotoxicity in murine neuronal HT22 cells. Our results demonstrated that glutamate resulted in cell death in a dose-dependent manner and supplementation of 100 nM sodium selenite prevented the detrimental effects of glutamate on cell survival. The glutamate induced cytotoxicity was associated with mitochondrial hyperpolarization, increased ROS production and enhanced oxygen consumption. Selenium reversed these alterations. Furthermore, glutamate increased the levels of mitochondrial fission protein markers pDrp1 and Fis1 and caused increase in mitochondrial fragmentation.

Dopamine protects agains glutamate by regulating calcium. “Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and neurodegenerative disease. Loss of calcium homeostasis is a key mediator of glutamate-induced cell death. The neurotransmitter dopamine (DA) is known to modulate calcium signalling, and here we show that it can do so in response to physiological concentrations of glutamate. Furthermore, DA is able to protect neurons from glutamate-induced cell death at pathological concentrations of glutamate. We demonstrate that DA has a novel role in preventing delayed calcium deregulation in cortical, hippocampal and midbrain neurons. The effect of DA in abolishing glutamate excitotoxicity can be induced by DA receptor agonists, and is abolished by DA receptor antagonists. Our data indicate that the modulation of glutamate excitotoxicity by DA is receptor-mediated. We postulate that DA has a major physiological function as a safety catch to restrict the glutamate-induced calcium signal, and thereby prevent glutamate-induced cell death in the brain.”

“These findings show that the mitochondrial SOD2 plays a critical role in protecting neuronal cells from glutamate-induced oxidative stress and cytotoxicity. These data also indicate that mitochodria are important early targets of glutamate-induced oxidative neurotoxicity.”

“Excess levels of glutamate, or other excitatory molecules, allow the calcium channel to remain open for a relatively long period of time. Calcium excess in the cytosol of the cell triggers the activation of inducible nitric oxide synthase and protein kinase C. The iNOS produces NO in excess, which begins to accumulate within the cell. When NO combines with the superoxide radical it forms the very destructive peroxynitrite radical. This radical is particularly injurious to the mitochondria, the chief source of energy for the neuron.5” (

These studies demonstrate that in addition to altering the bioenergetic properties of mitochondria, neurotoxins can also alter mitochondrial movement and morphology. We speculate that neurotoxin-mediated impairment of mitochondrial delivery may contribute to the inju- rious effects of neurotoxins.

“Increasing energy production, using coenzyme Q-10,, L-carnitine, alpha-lipoic acid, and other metabolic precursors and substrates can significantly reduce glutamate excitotoxic damage.”

“Furthermore, the attenuation of mitochondrial damage induced by pyruvate was partly reduced by 3-methyladenine. This suggested autophagy mediated pyruvate protection by preventing mitochondrial damage. Taken together, pyruvate protects cells from glutamate excitotoxicity by regulating DAPK1 complexes, both through dissociation of DAPK1 from NMDA receptors and association of DAPK1 with Beclin-1. They go forward to protect cells by attenuating Ca2+ overload and activating autophagy. Finally, a convergence of the two ways protects mitochondria from glutamate excitotoxicity, which leads to cell survival.”

“Likewise, there is an intimate interrelationship between excitotoxicity, inflammatory cytokines. free radical generation. lipid peroxidation, and abnormalities in calcium homeostasis, which occur in an autocrine manner. Central in this process is dysfijnction of mitochondria, which also increases the generation of free radicals (particularly peroxynitrite) and dramatically increases sensitivity to extracellular glutamate to the extent that even physiological levels ofglutamate can be excitotoxic. As chronic inflammatory change takes place in the brain, secondary suppression of mitochondria occurs as a result of isch- emia/hypoxia. This also increases sensitivity to excitotoxicity by reducing cellular energy production, which further aggravates disruptions of calcium homeostasis. In the developing brain, a loss of calcium oscillation caused by excitotoxic and androgen- induced calcium excess impairs progenitor cell migration and diflerentiation.”


The following symptoms may indicate that your child has mitochondrial dysfunction or a problem in energy production.

  • Large motor delays
  • Failure to thrive, growth delays
  • Low muscle tone
  • Extreme fatigue
  • Inability to regulate temperature
  • Autistic symptoms
  • Global muscle weakness

Difficulty waking”