Stress-perturbed mitochondrial dysfunction

By: James V. Kohl | Published on: November 21, 2015

Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress


To visualize the stress-reactive profiles across genotypes, a heat map with hierarchical clustering of the mean relative difference “stress–resting” was generated, demonstrating that each mitochondrial defect induced a different amino acid response signature (Fig. 4F). In particular, the stress-reactive amino acid profile was most distinct in mice with the respiratory chain complex I ND6 defect. To determine which class of amino acids was most discriminatory between mitochondrial defects, a partial least squares discriminant analysis (PLSDA) was conducted, identifying ornithine,  lysine, and arginine (of variable importance in projection scores >1) as major contributors to genotype differences. This trio of dibasic amino acids is specifically involved in the mitochondria-associated urea cycle for the deamination of biomolecules (36).

Reported as:  Study connects mitochondria to psychological stress response and species resilience

Though no rigorous studies have previously examined whether mitochondria modulate an organism’s psychological stress response, there are three reasons for the hypothesis that they do: First, requirements for ATP must be increased to face stress-induced cellular perturbations. Second, mitochondria generate reactive metabolic intermediates and reactive oxygen species (ROSs) during electron flow, which leads to oxidative stress in the absence of sufficient antioxidants. The generation of these constituents is a signal of adaptation, altering gene expression, which means that the stress-induced epigenetic changes observed in the hippocampus could be a result of mitochondrial activity. And third, stress-induced physiological responses like insulin resistance, inflammation and others can be triggered by mitochondrial dysfunction alone. So mitochondria are a likely hub of stress response and modulation.

Excerpt 2)

…based on this model, it seems that mitochondria lie at the interface of genetic and environmental factors that shape an organism’s evolution. They suggest that future research targeting mitochondria can contribute to biological resilience, psychological health, and response to environmental stressors.

My comment: Bruce McEwen coauthored this article about how ecological variation is linked to nutrient-dependent ecological adaptation via amino acid substitutions. In the early 90’s, he taught me to start my model with gene activation in GnRH neurosecretory neurons.
Since then, I have detailed the facts about epigenetically-effected changes in the vertebrate hypothalamic GnRH pulse, which link food odors and pheromones to RNA-mediated cell type differentiation in species from microbes to man. What is known about RNA-mediated gene duplication and RNA-mediated amino acid substitutions links biophysically constrained protein folding chemistry and fixed amino acid substitutions to morphological and behavioral phenotypes in all living genera via microRNAs, and cell adhesion proteins that protect organized genomes from stress-induced “heat shock.” Supercoiled DNA links the epigenetic landscape to protection against stress related virus-induced heat shock that prevents nutrient energy-dependent RNA-mediated cell type differentiation.  
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My comment: The thermodynamic cycles of protein biosynthesis and degradation link nutrient stress and social stress to adaptations that must occur at the level of supercoiled DNA that links the mitochondria to prevention of stress-perturbed protein folding, which links viruses to mutations and genomic entropy.
Earlier today I learned that I am not the only researcher who is currently focused on the dissemination of accurate information about virus-perturbed protein folding and pathology. It is a great relief to know that others will help to force neo-Darwinian theorists to do what Bruce McEwen taught me to do more than two decades ago:  Start with gene activation!
If not, your model cannot link atoms to ecosystems via the gene-cell-tissue-organ-organ system pathway that all molecular biologists know links molecular epigenetics and genetics via metabolic networks and genetic networks in species from microbes to man.
See also: Epigenetics and Animal Virus InfectionsFrontiers Research Topic

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