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In last decade, investigations of mitochondria including their various reduced forms such as hydrogenosomes and mitosomes revealed unexpected diversity of this indispensable organelle. Interestingly, the single mitochondrion of parasitic protist Trypanosoma brucei is able to undergo remarkable functional and structural changes reflecting available carbon sources. Moreover, it was proposed that trypanosomes belong among the most ancient eukaryotes and as such, their mitochondria raised high attention of biologists. To contribute to the knowledge of mitochondrial biogenesis and function, we focused on studies of two key mitochondrial processes, the processing of preproteins that are imported to the mitochondria, and mechanism of pyruvate transport to these organelles. Moreover, we also investigated uptake of iron by T. brucei. This metal is essential for function of numerous proteins, particularly for iron-sulfur proteins in mitochondria. Evolutionary history of trypanosomes and their mitochondrion is a question of debates. According to some reports, mitochondrion of trypanosomes represent an ancient form of this organelle, which is supported by identification of putative "archaic" translocase of the outer mitochondrial membrane (ATOM) and finding of only a single type of translocation pore in...

Peroxisomes and mitochondria play a key role in oxygen metabolism. It was widely accepted that the evolutionary adaptation of eukaryotes to anaerobiosis is reflected by the metabolic reduction of mitochondria, and concomitant loss of peroxisomes. The anaerobic protists Mastigamoeba balamuthi (Mb), Pelomyxa schiedti (Ps), and Entamoeba histolytica (Eh) contradict this paradigm. They possess anaerobic types of mitochondria (hydrogenosomes, mitosomes) but also host "anaerobic peroxisomes". Mb/Ps peroxisomes contain a common set of 13 peroxins (Pexs) that retain the core members of each functional category including components of both PTS1 and PTS2 machinery for matrix protein import. However, Eh peroxisomes harbour a reduced set of 7 known Pexs and lacks several components that are highly conserved among most eukaryotic lineages, including components of PTS2 machinery (Pex7), the RING complex (Pex2/10/12), docking complex (Pex13), and peroxisomal membrane protein import receptor (Pex3). Concerning the functional annotation, no clear biochemical context has been found in these anaerobic peroxisomes. They are diverse in enzymatic contents and are involved in various metabolic reactions, while catalase and typical peroxisomal enzymes of fatty acid beta-oxidation are absent. Mb peroxisomes appear to be involved in...

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Chloramphenicol has been used to study mitochondrial biogenesis in mammalian cells by examining its effect on: the incorporation of radioactive amino acids into protein by isolated mitochondria, the growth of L cells, the level of representative enzymes and cytochromes in the mitochondria and cytoplasm and the structure of mitochondria and L cells. A reversible inhibition of synthesis of cytochrome c oxidase was obtained by treating cells with D-threo-chloramphenicol for 90 hr. Recovery of cytochrome c oxidase activity was inhibited by cycloheximide, an inhibitor of cytoplasmic protein synthesis. Cycloheximide also reversibly inhibited cytochrome c oxidase formation in cells which were not treated with D-chloramphenicol. It is suggested that the mitochondria and the nucleus have a joint control in the formation of a functionally active cytochrome c oxidase enzyme. / Thesis / Doctor of Philosophy (PhD)

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Yes / Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis.