Mitochondrial Outer Membrane Proteome of Trypanosoma brucei Reveals Novel Factors Required to Maintain Mitochondrial Morphology

Niemann, Moritz; Wiese, Sebastian; Mani, Jan; Chanfon, Astrid; Jackson, Christopher; Meisinger, Christof; Warscheid, Bettina; Schneider, André (2013). Mitochondrial Outer Membrane Proteome of Trypanosoma brucei Reveals Novel Factors Required to Maintain Mitochondrial Morphology. Molecular & cellular proteomics, 12(2), pp. 515-528. Bethesda, Md.: American Society for Biochemistry and Molecular Biology 10.1074/mcp.M112.023093

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Trypanosoma brucei is a unicellular parasite that causes devastating diseases in humans and animals. It diverged from most other eukaryotes very early in evolution and, as a consequence, has an unusual mitochondrial biology. Moreover, mitochondrial functions and morphology are highly regulated throughout the life cycle of the parasite. The outer mitochondrial membrane defines the boundary of the organelle. Its properties are therefore key for understanding how the cytosol and mitochondria communicate and how the organelle is integrated into the metabolism of the whole cell. We have purified the mitochondrial outer membrane of T. brucei and characterized its proteome using label-free quantitative mass spectrometry for protein abundance profiling in combination with statistical analysis. Our results show that the trypanosomal outer membrane proteome consists of 82 proteins, two-thirds of which have never been associated with mitochondria before. 40 proteins share homology with proteins of known functions. The function of 42 proteins, 33 of which are specific to trypanosomatids, remains unknown. 11 proteins are essential for the disease-causing bloodstream form of T. brucei and therefore may be exploited as novel drug targets. A comparison with the outer membrane proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three outer membrane proteins of unknown function resulted in a collapse of the network-like mitochondrion of procyclic cells and for the first time identified factors that control mitochondrial shape in T. brucei.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR) > Unit Childrens Hospital > Forschungsgruppe Humangenetik

UniBE Contributor:

Niemann, Moritz; Mani, Jan; Chanfon, Astrid; Jackson, Christopher; Meisinger, Christof and Schneider, André

Subjects:

500 Science > 540 Chemistry
500 Science > 570 Life sciences; biology

ISSN:

1535-9476

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

André Schneider

Date Deposited:

10 Dec 2013 22:10

Last Modified:

06 Dec 2014 06:09

Publisher DOI:

10.1074/mcp.M112.023093

BORIS DOI:

10.7892/boris.39292

URI:

https://boris.unibe.ch/id/eprint/39292

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