A conserved mitochondrial outer membrane protein mediates kDNA maintenace in Trypanosoma brucei

Schnarwiler, Felix (21 April 2013). A conserved mitochondrial outer membrane protein mediates kDNA maintenace in Trypanosoma brucei (Unpublished). In: 5th Kinetoplastid Molecular Cell Biology Meeting. Woodshole, MA, USA. 21.-25.04.2014.

Kinetoplastids are defined by the unique organization of their mitochondrial DNA (kDNA). It forms a highly concatenated DNA network that is linked to the basal body of the flagellum by the tripartite attachment complex (TAC). The TAC encompasses intra and extramitochondrial filaments and a highly differentiated region of the two mitochondrial membranes. Here we identify and characterize a mitochondrial outer membrane protein of Trypanosoma brucei that is predominantly localized in the TAC. The protein is essential for growth in both life cycle stages. Immunofluorescence shows that ablation of the protein does not affect kDNA replication but abolishes the segregation of the replicated kDNA network causing rapid loss of kDNA. Besides its role in kDNA maintenance in vivo and in vitro experiments show that the protein is involved in mitochondrial protein import and that it interacts with a recently discovered protein import factor. RNAi experiments in a T. brucei cell line in which the kDNA is dispensable suggest that the essential function is linked to kDNA maintenance. Bioinformatic analysis shows that the studied outer membrane protein has beta-barrel topology and that it belongs to the mitochondrial porin family comprising VDAC, Tom40 and Mdm10. Interestingly, Mdm10 has so far only been found in yeast. Its function in protein import and mitochondrial DNA maintenance suggests that the protein in our study is the functional homologue of Mdm10. Thus, the TAC – a defining structure of Kinetoplastids – contains a conserved protein which in yeast and trypanosomes performs the same function. Our study therefore provides an example that trypanosomal biology, rather than being unique, often simply represents a more extreme manifestation of a conserved biological concept.

Item Type:

Conference or Workshop Item (Speech)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Schnarwiler, Felix

Subjects:

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

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

05 Aug 2014 09:55

Last Modified:

05 Dec 2022 14:36

URI:

https://boris.unibe.ch/id/eprint/57512

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