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Study of mitochondrial morphology in pancreatic β-cells depending on the presence of different types of secretagogues
Lorenc, David ; Dlasková, Andrea (advisor) ; Mráček, Tomáš (referee)
Glucose homeostasis is crucial for the proper functioning of the organism. The pancreatic β-cells, which serve as a sensor of changes in blood glucose concentration and are responsible for the adequate release of the hormone insulin, play a crucial role in its maintenance. Increased glucose concentration activates oxidative phosphorylation and subsequently increases the concentration of cellular ATP, which then indirectly stimulates insulin secretion. The process of oxidative phosphorylation is localized in the inner mitochondrial membrane, where the final stage of processing of substrate energy into ATP occurs. To make the oxidative phosphorylation process as efficient as possible, the mitochondrial network undergoes a series of morphological changes. In this work, we aimed to elucidate the effect of changes in nutrient concentration on mitochondrial morphology in a pancreatic β-cell model, the INS1E tissue line. We used as experimental conditions: 1) a high glucose concentration at which insulin secretion is maximal, 2) a low glucose concentration at which insulin secretion does not occur, and 3) the addition of α-ketoisocaproate, a leucine metabolite that amplifies insulin secretion. We first characterized the bioenergetic parameters that influence mitochondrial morphology. A decrease in glucose...
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The inner mitochondrial membrane cristae biogenesis
Efimova, Iuliia ; Mráček, Tomáš (advisor) ; Petrů, Markéta (referee)
Invaginations of the inner mitochondrial membrane originate cristae - important structural and bioenergetic mitochondrial compartments. Long-term observations of mitochondrial ultrastructure uncovered cristae dynamics, but did not identify mechanisms of cristae formation and maintenance. This thesis summarizes results of latest research on molecular mechanisms of mitochondrial cristae biogenesis, which are conserved from fungi to mammals including human. The emphasis is put on major remodeling factors: F1Fo-ATP synthase dimers, MICOS complex, OPA1 protein and cardiolipin. Their defects lead to extensive changes on cristae level, as well as on mitochondrial, cellular and organismal levels. Various pathophysiological conditions and human mitochondrial diseases are related to these defects. More detailed research of cristae biogenesis is therefore of high significance, new findings could assist in the development of new treatments for mitochondrial disorders.
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New components and functions of mitochondrial ATP synthase.
Ho, Dieu Hien ; Pecina, Petr (advisor) ; Kalous, Martin (referee)
The system of oxidative phosphorylation, or respiratory chain in mitochondria gives the eukaryotic cell total majority of the energy it receives and uses in the form of ATP. F1Fo-ATP synthase, powered by the proton-motive force is directly responsible for the ATP synthesis. Diseases connected to the ATP synthesis can have even lethal consequences. There is therefore no doubt about the need for a detailed analysis of the structure of this enzyme. What is left is to reveal the structure of the transmembrane domains, which are not involved in the synthesis itself, but they can for example work as stabilisers or assembly factors. Outside the synthesis activity the dimers of F1Fo-ATP synthase are apparently taking part in the formation of the cristae of the inner membrane of a mitochondrion. Recently, the role of the enzyme is also considered in the creation of the mitochondrial permeability transition pore.
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The Diverged Trypanosome MICOS Complex as a Hub for Mitochondrial Cristae Shaping and Protein Import
HELLER, Jiří
This work deals with MICOS, which stands for mitochondrial contact site and cristae organization system. Until now this multiprotein complex has been analyzed experimentally only in yeast and mammals, who belong to the supergroup Opisthokonta. Our study was done on the parasitic protist T. brucei, a member of the another supergroup called Excavata, which is very diverged from opisthokonts.Thus, it is the very first study done outside of Opisthokonta. This could be very useful in the future for a comparative analysis approach. Our results show that the MICOS complex in T. brucei is composed of 9 subunits, most of which are essential for normal growth. It is required for the maintenance of discoidal cristae that typify excavates such as kinetoplastids and euglenids and mediating the mitochondrial outer and inner membranes contacts. In addition, we discovered that the mitochondrial contact site and cristae organization system may participate in the intermembrane space protein import and help in the oxydative phosphorylation complex formation. It seems that this interesting complex is involved in even more cellular processes.
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The inner mitochondrial membrane cristae biogenesis
Efimova, Iuliia ; Mráček, Tomáš (advisor) ; Petrů, Markéta (referee)
Invaginations of the inner mitochondrial membrane originate cristae - important structural and bioenergetic mitochondrial compartments. Long-term observations of mitochondrial ultrastructure uncovered cristae dynamics, but did not identify mechanisms of cristae formation and maintenance. This thesis summarizes results of latest research on molecular mechanisms of mitochondrial cristae biogenesis, which are conserved from fungi to mammals including human. The emphasis is put on major remodeling factors: F1Fo-ATP synthase dimers, MICOS complex, OPA1 protein and cardiolipin. Their defects lead to extensive changes on cristae level, as well as on mitochondrial, cellular and organismal levels. Various pathophysiological conditions and human mitochondrial diseases are related to these defects. More detailed research of cristae biogenesis is therefore of high significance, new findings could assist in the development of new treatments for mitochondrial disorders.
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New components and functions of mitochondrial ATP synthase.
Ho, Dieu Hien ; Pecina, Petr (advisor) ; Kalous, Martin (referee)
The system of oxidative phosphorylation, or respiratory chain in mitochondria gives the eukaryotic cell total majority of the energy it receives and uses in the form of ATP. F1Fo-ATP synthase, powered by the proton-motive force is directly responsible for the ATP synthesis. Diseases connected to the ATP synthesis can have even lethal consequences. There is therefore no doubt about the need for a detailed analysis of the structure of this enzyme. What is left is to reveal the structure of the transmembrane domains, which are not involved in the synthesis itself, but they can for example work as stabilisers or assembly factors. Outside the synthesis activity the dimers of F1Fo-ATP synthase are apparently taking part in the formation of the cristae of the inner membrane of a mitochondrion. Recently, the role of the enzyme is also considered in the creation of the mitochondrial permeability transition pore.
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