The Mba1 homologue of Trypanosoma brucei is involved in the biogenesis of oxidative phosphorylation complexes

Wenger, C.; Harsman, A.; Niemann, M.; Oeljeklaus, S.; von Känel, C.; Calderaro, S.; Warscheid, B.; Schneider, A.

doi:10.1101/2022.12.21.521360

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bioRxiv · 10.1101/2022.12.21.521360

The Mba1 homologue of Trypanosoma brucei is involved in the biogenesis of oxidative phosphorylation complexes

Wenger, C.·Harsman, A.·Niemann, M.·Oeljeklaus, S.·von Känel, C.·Calderaro, S.·Warscheid, B.·Schneider, A.

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Abstract

Consistent with other eukaryotes, the Trypanosoma brucei mitochondrial genome encodes mainly hydrophobic core subunits of the oxidative phosphorylation system. These proteins must be co-translationally inserted into the inner mitochondrial membrane and are synthesized by the highly divergent trypanosomal mitoribosomes, which have a much higher protein to RNA ratio than any other ribosome. Here, we show that the trypanosomal ortholog of the mitoribosome receptor Mba1 (TbMba1) is essential for normal growth of procyclic trypanosomes but redundant in the bloodstream form, which lacks an oxidative phosphorylation system. Proteomic analyses of TbMba1-depleted mitochondria from procyclic cells revealed reduced levels of many components of the oxidative phosphorylation system, most of which belong to the cytochrome c oxidase (Cox) complex, three subunits of which are mitochondrially encoded. However, the integrity of the mitoribosome and its interaction with the inner membrane were not affected. Pulldown experiments showed that TbMba1 forms a dynamic interaction network that includes the trypanosomal Mdm38/Letm1 ortholog and a trypanosome-specific factor that stabilizes the CoxI and CoxII mRNAs. In summary, our study suggests that the function of Mba1 in the biogenesis of membrane subunits of OXPHOS complexes is conserved among yeast, mammalian, and trypanosomes, which belong to two eukaryotic supergroups.

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Wenger, C., Harsman, A., Niemann, M., Oeljeklaus, S., von Känel, C., Calderaro, S., Warscheid, B., Schneider, A.. 2022-12-21. The Mba1 homologue of Trypanosoma brucei is involved in the biogenesis of oxidative phosphorylation complexes. https://doi.org/10.1101/2022.12.21.521360

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