Identification of a novel and ancestral machinery involved in mitochondrial membrane branching in Trypanosoma brucei

Morel, C. A.; Asencio, C.; Blancard, C.; Salin, B.; Gontier, E.; Duvezin-Caubet, S.; Rojo, M.; Bringaud, F.; Tetaud, E.

doi:10.1101/2023.06.28.546890

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bioRxiv · 10.1101/2023.06.28.546890

Identification of a novel and ancestral machinery involved in mitochondrial membrane branching in Trypanosoma brucei

Morel, C. A.·Asencio, C.·Blancard, C.·Salin, B.·Gontier, E.·Duvezin-Caubet, S.·Rojo, M.·Bringaud, F.·Tetaud, E.

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Abstract

Unlike most other eukaryotes, where mitochondria continuously fuse and divide, the mitochondrion of trypanosome cells forms a single and continuously interconnected network that divides only during cytokinesis. However, the machinery governing mitochondrial remodeling and interconnection of trypanosome mitochondrion remain largely unknown. We functionally characterize a novel dynamin-superfamily protein (DSP) from T. brucei (TbMfnL) which shares close similarity with a family of homologs present in various eukaryotic and prokaryotic phyla, but not in opisthokonts like mammals and budding yeast. The sequence and domain organization of TbMfnL is distinct and it is phylogenetically very distant from the yeast and mammalian dynamin-related proteins involved in mitochondrial fusion/fission dynamincs, such as Opa1 and Mfn. TbMfnL localizes to the inner mitochondrial membrane facing the matrix, and upon overexpression, induces a strong increase in the interconnection and branching of mitochondrial filaments in a GTPase-dependent manner. TbMfnL is a component of a novel membrane remodeling machinery with an unprecedented matrix-side localization that is able to modulate the degree of intermitochondrial connections.

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Morel, C. A., Asencio, C., Blancard, C., Salin, B., Gontier, E., Duvezin-Caubet, S., Rojo, M., Bringaud, F., Tetaud, E.. 2023-06-28. Identification of a novel and ancestral machinery involved in mitochondrial membrane branching in Trypanosoma brucei. https://doi.org/10.1101/2023.06.28.546890

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