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The Mitochondrial Contact Site and Cristae Organization System and F1FO-ATP Synthase Crosstalk is a Fundamental Property of Mitochondrial Cristae
CADENA, Lawrence Rudy
The acquisition of mitochondria from an endosymbiont closely related to extant alphaproteobacteria occurred prior to the divergence of modern eukaryotes. Since then, diverse eukaryotes have not only developed a number of different mechanisms to adapt to their environment regarding growth and proliferation, but perpetuated certain traits that have persisted for eons. This thesis postulates an ancestral mechanism for cristae development in mitochondria involving interplay between two cristae shaping protein complexes, the Mitochondrial Contact Site and Cristae Organization System and F1FO-ATP Synthase, that has remained conserved throughout eukaryotic diversification for over 2 billion years.
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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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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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Export of biomolecules from mitochondria
Pelc, Josef ; Doležal, Pavel (advisor) ; Kovalčíková, Jana (referee)
Mitochondrion is cellular organelle evolved from the endosymbiotic bacteria. Because of its bacterial origin mitochondrion has a number of unique properties and metabolic pathways. Mitochondria or its reduced forms are present in all eukaryotic organisms except a single exception. During the course of evolution most of mitochondrial DNA was transferred to the nucleus. Despite this, mitochondria still encode several proteins that are part of the electron transport chain and the ATP synthase. These proteins are transported from the mitochondrial matrix into the inner mitochondrial membrane. Misfolded proteins of the inner membrane are degraded by mitochondrial proteases, which leads to the release of generated peptides. Fe-S clusters are assembled in the mitochondrial matrix. Still unknown molecule, which is product of ISC pathway is transported into cytosol and participates in the assembly of cytosolic and nuclear iron-sulfur proteins. Other transport pathway ensures the exchange of lipids between the endoplasmic reticulum and mitochondria. Both mitochondrial membranes have different lipid composition. To maintain their properties specific lipid transport is required between the two mitochondrial membranes. This transport pathway is also used for the lipid synthesis in the inner mitochondrial membrane.
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