Publications (78) View all
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Article: Unique aspects of mitochondrial biogenesis in trypanosomatids.
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ABSTRACT: Mitochondrial biogenesis consists of the sum of all processes required for the formation of the mitochondrial membranes as well as the soluble compartments they contain. Furthermore, it includes the replication of the mitochondrial genome and correct segregation of the organelles during cell division. Mitochondrial proteins come from two sources, a limited but essential set of inner membrane proteins is encoded by the mitochondrial genome, whereas the large majority (90-95%) is derived from nucleus-encoded genes and are posttranslationally imported into the organelle. Trypanosomatids belong to the earliest diverging branches of the eukaryotic evolutionary tree which have mitochondria. This is reflected in the organisation of their mitochondrial DNA that consists of a network of two classes of topologically interlocked circular DNA molecules as well as many unique features in their mitochondrial biogenesis. The proteins encoded on the mitochondrial genome are conventional for a mitochondrial genome, their expression, however, involves a complex series of processes. Many genes represent incomplete open reading frames and their primary transcripts have to remodelled by RNA editing to convert them into translatable mRNAs. RNA editing is mediated by small mitochondria-encoded transcripts, the guide RNAs, and is in that form specific for trypanosomatids and closely related organisms. Mitochondrial translation is also unconventional. No tRNA genes are encoded on the mitochondrial genome. Instead, mitochondrial protein synthesis functions exclusively with imported cytosolic, eukaryotic-type tRNAs. The composition of mitochondrial ribosomes is also unusual in that they contain the smallest known rRNAs. They are about 30% shorter than the already much reduced rRNAs in human mitochondria. Furthermore, the topological organisation of the mitochondrial genome requires an elaborate replication machinery involving topoisomerases. Finally, some trypanosomatids have life cycle stages exhibiting very different mitochondrial activities and can therefore serve as a model system for the regulation of mitochondrial biogenesis.International Journal for Parasitology 12/2001; 31(13):1403-15. · 3.39 Impact Factor -
Article: Does the evolutionary history of aminoacyl-tRNA synthetases explain the loss of mitochondrial tRNA genes?
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ABSTRACT: The importation of cytosolic tRNAs is required for protein synthesis in the mitochondria of the wide variety of eukaryotes that lack a complete set of mitochondrial tRNA genes. The evolutionary history of the process, however, is still enigmatic. The analysis presented here suggests that the loss of distinct mitochondrial tRNA genes was not random and that it might be explained by the differential capabilities of mitochondrial aminoacyl-tRNA synthetases to charge imported eukaryotic-type tRNAs with amino acid.Trends in Genetics 11/2001; 17(10):557-9. · 10.06 Impact Factor -
Article: Mitochondrial tRNA import: are there distinct mechanisms?
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ABSTRACT: Sequence information from an increasing number of complete mitochondrial genomes indicates that a large number of evolutionary distinct organisms import nucleus-encoded tRNAs. In the past five years, much research has been initiated on the features of imported tRNAs, the mechanism and the energetics of the process as well as on the components of the import machinery. In summary, these studies show that the import systems of different species exhibit some unique features, suggesting that more than one mechanism might exist to import tRNAs.Trends in Cell Biology 01/2001; 10(12):509-13. · 12.35 Impact Factor -
Article: ATP production in isolated mitochondria of procyclic Trypanosoma brucei.
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ABSTRACT: Membrane potential-dependent ATP production was measured in mitochondrial fractions of procyclic Trypanosoma brucei using a luciferase based assay. Mitochondria isolated under hypotonic conditions were able to produce ATP using succinate as substrate. The same was observed with mitochondria isolated under isotonic conditions, however, in this case a 6-7-fold higher amount of ATP was produced with glycerol-3-phosphate as substrate. Disruption of the outer membrane of isotonically prepared mitochondria lead to a selective loss of the glycerol-3 phosphate induced ATP production, indicating that glycerol-3-phosphate dehydrogenase is a soluble enzyme of the intermembrane space. Isolation of mitochondria under hypotonic conditions, therefore, results in disruption of the outer membrane, whereas in the organelles isolated under isotonic conditions both the membranes remain intact.Molecular and Biochemical Parasitology 12/2000; 111(1):87-94. · 2.55 Impact Factor -
Article: Chloramphenicol-sensitive mitochondrial translation in Trypanosoma brucei.
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ABSTRACT: We developed an in organello system to label newly synthesized mitochondrially encoded proteins of Trypanosoma brucei. Highly purified mitochondria, prepared under isotonic conditions, were incubated with radioactive methionine and cysteine in a suitable translation buffer. Analysis of mitochondrial extracts on TRIS-Tricine gels revealed a subset of labeled, NP-40-insoluble proteins. The labeling of these proteins was resistant to the cytosol-specific translation inhibitor cycloheximide. The proteins, however, were not labeled in the presence of chloramphenicol or erythromycin, inhibitors of prokaryotic type translation, or puromycin, a general translation inhibitor. These results indicate that isotonically isolated mitochondria of T. brucei are capable of protein synthesis.Parasitology Research 09/1999; 85(8-9):779-82. · 2.15 Impact Factor
