Disturbed Mitochondrial Metabolism Research Articles

СТРУКТУРНО-ФУНКЦИОНАЛЬНЫЕ ПРОЯВЛЕНИЯ ОСТРОГО И ХРОНИЧЕСКОГО ГРАВИТАЦИОННОГО СТРЕССА В НАДПОЧЕЧНИКЕ

Optical and electron microscopy, quantitative cytochemistry and morphometric analysis were used to look into structural and functional transformations in the bloodstream, adrenal cortex corticosterocytes and adrenal brain cells in consequence of exposure to modeled acute and chronic gravitational stresses (AGS and CGS respectively). AGS caused adrenal hyperemia, hypertrophy of the zona fasciculata, elevated activity of enzymes involved in mitochondrial and extramitochondrial oxidation, and secretion of undissolved catecholamine granules in the capillary bloodstream. CGS depressed mitochondrial oxidation, activated glycolysis, produced destructive changes in corticosteroids, and LED lipid droplets in capillary lumen. From capillaries the fat droplets traveled further to the brain sinusoids where they deposited together with blood corpuscles (erythrocytes primarily) and formed microcirculation impairing microemboli. Thereupon we assume that the source of lipid droplets under the full-strength gravitational stress is intermediate products of corticoid synthesis in conditions of mitochondria destruction and disturbed mitochondrial metabolism in cells of the fasciculata and glomerulosa zones.

Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency

Background Sedoheptulose, arabitol, ribitol, and erythritol have been identified as key diagnostic metabolites in TALDO deficiency. Method Urine from 6 TALDO-deficient patients and TALDO-deficient knock-out mice were analyzed using 1H-NMR spectroscopy and GC–mass spectrometry. Results Our data confirm the known metabolic characteristics in TALDO-deficient patients. The β-furanose form was the major sedoheptulose anomer in TALDO-deficient patients. Erythronic acid was identified as a major abnormal metabolite in all patients and in knock-out TALDO mice implicating an as yet unknown biochemical pathway in this disease. A putative sequence of enzymatic reactions leading to the formation of erythronic acid is presented. The urinary concentration of the citric acid cycle intermediates 2-oxoglutaric acid and fumaric acid was increased in the majority of TALDO-deficient patients but not in the knock-out mice. Conclusion Erythronic acid is a novel and major hallmark in TALDO deficiency. The pathway leading to its production may play a role in healthy humans as well. In TALDO-deficient patients, there is an increased flux through this pathway. The finding of increased citric acid cycle intermediates hints toward a disturbed mitochondrial metabolism in TALDO deficiency.

Is atherosclerosis a mitochondrial disorder?

There is increasing evidence that damage to the vascular environment from oxidative stress plays a major role in the pathogenesis of atherosclerosis in addition to classical risk factors, such as age, arterial hypertension, diabetes, dyslipidemia, smoking, vascular wall inflammation, or genetic predisposition. Oxidative stress results from the endogenous or exogenous generation of reactive oxidative or nitrogen species, generated by the respiratory chain or enzymatic sources. Oxidative stress results in lipid peroxidation, damage of mitochondrial components including mitochondrial DNA, mitochondrial dysfunction, damage of endothelial cells, vascular smooth muscle cells, and erythrocytes, and lastly apoptosis via either the receptor-mediated pathway or the mitochondria-mediated pathway and activation of the caspase cascade. Though re-balancing of the redox homeostasis by various agents is clinically hardly effective, various trials with experimental agents are promising in this respect. Overall, atherosclerosis appears to be the endpoint of various different pathogenetic mechanisms, of which oxidative stress and disturbed mitochondrial metabolism and function are key factors.