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Mechanisms of iron-sulfur cluster biogenesis in eukaryotes
Temešinko, Tomáš ; Doležal, Pavel (advisor) ; Malych, Ronald (referee)
Many essential cellular proteins use iron-sulfur (Fe-S) clusters as cofactors. These proteins often serve as enzymes, components of the electron-transport chain or as intracellular sensors. Prior to the use of the cluster in a protein, it needs to be formed or created de novo. In total, four different mechanisms of Fe-S cluster biogenesis can be used by the eukaryotic cell - ISC, CIA, SUF and NIF. All of these pathways include a specific targeting system for delivering the cluster to its acceptor protein. Errors in biosynthesis ofFe-Sclustersaremostlylethalandcanleadtofailureindevelopmentofmulticellularorganisms.Despite this a better characterization of these mechanisms is needed as research is currently still in progress. This bachelor's thesis provides current information regarding the mechanisms of Fe-S clusters biogenesis in eukaryotes acquired mostly from mammalian cells, including humans, and from well-known model organisms such as Saccharomyces cerevisiae, Arabidopsis thaliana, and parasitic protist Giardia intestinalis.
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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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