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Yeast retrograde signaling pathway between mitochondria and the nucleus
Podholová, Kristýna ; Palková, Zdena (advisor) ; Fraiberk, Martin (referee)
Retrograde signaling pathway is the pathway between mitochondria and nucleus. This pathway helps Saccharomyces cerevisiae to cope with worsening of conditions of life, such as depletion of rich nutrient sources and necessity of use poor resources, reduction of mitochondrial membrane potential, or loss of mitochondrial DNA causing disturbances in the citric acid cycle. Most of these conditions are associated with aging yeast populations. Key retrograde pathway proteins include RTG transcription factors Rtg1p/Rtg3p and cytoplasmic protein Rtg2p. Retrograde pathway is upregulated by several positive and negative regulators including the TOR pathway, which negatively regulates retrograde pathway. The retrograde pathway target genes include genes coding for tricarboxylic cycle enzymes, peroxisomal enzymes, transporters and other enzymes of anaplerotic pathways. Retrograde response help cells to modify their metabolism so that they are able to overcome unfavorable environmental conditions in which they live. Powered by TCPDF (www.tcpdf.org)
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The effect of psychotropic drugs on the mitochondrial functions.
Cikánková, Tereza ; Rečková Hroudová, Jana (advisor) ; Herink, Josef (referee) ; Vaňhara, Petr (referee)
Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...
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Yeast retrograde signaling pathway between mitochondria and the nucleus
Podholová, Kristýna ; Palková, Zdena (advisor) ; Fraiberk, Martin (referee)
Retrograde signaling pathway is the pathway between mitochondria and nucleus. This pathway helps Saccharomyces cerevisiae to cope with worsening of conditions of life, such as depletion of rich nutrient sources and necessity of use poor resources, reduction of mitochondrial membrane potential, or loss of mitochondrial DNA causing disturbances in the citric acid cycle. Most of these conditions are associated with aging yeast populations. Key retrograde pathway proteins include RTG transcription factors Rtg1p/Rtg3p and cytoplasmic protein Rtg2p. Retrograde pathway is upregulated by several positive and negative regulators including the TOR pathway, which negatively regulates retrograde pathway. The retrograde pathway target genes include genes coding for tricarboxylic cycle enzymes, peroxisomal enzymes, transporters and other enzymes of anaplerotic pathways. Retrograde response help cells to modify their metabolism so that they are able to overcome unfavorable environmental conditions in which they live. Powered by TCPDF (www.tcpdf.org)
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Mitochondrial subpopulations in rat myocardium - effect of chronic hypoxia
Kovalčíková, Jana ; Nováková, Olga (advisor) ; Žurmanová, Jitka (referee)
Adaptation to chronic hypoxia induces endogenous cardioprotection and increases the heart resistance to ischemia/reperfusion injury. The heart mitochondria, which produce reactive oxygen species (ROS) in addition to ATP, play an important role in these processes. During ischemia/reperfusion, ROS are produced in excessive amounts and damage the cells. However, in lower concentrations, ROS are involved in the signalling pathway of cardioprotection induced by adaptation to chronic hypoxia. In the heart, two mitochondrial subpopulations have been observed, subsarcolemmal mitochondria (SSM) and intermyofibrillar mitochondria (IMFM), which differ in cell localization as well as in morphological and biochemical properties. The aim of this work was to introduce the method of SSM and IMFM isolation in our laboratory and to analyse their antioxidative capacity after adaptation to chronic hypoxia. Adult male Wistar rats were kept either under normoxic conditions or exposed to intermittent high-altitude hypoxia (IHA; 7000 m, 5 days a week/8 hours a day, totally 25 exposures). Mitochondrial subpopulations were isolated from heart left ventricle and their functionality was verified by measuring oxygen consumption and enzyme activities. The IMFM had higher oxygen consumption in comparison with SSM and activities...
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