New Essential Trypanosomal TIM Component

Mitochondria import nearly all of their proteins using inner membrane protein translocases (TIMs). Opposite to other eukaryotes, trypanosomes only have one type of TIM. The Schneider  and Warscheid labs could now identify a new essential component of this TIM, the protein TbTim15. They could show that it lacks transmembrane domains and localizes to the intermembrane space. It is essential to import both categories byof transported proteins and required by the procyclic as well as the bloodstream form. The researchers speculate that TbTim15 could be the import receptor for TIM itself. Their findings have been published in the article "Intermembrane space-localized TbTim15 is an essential subunit of the single mitochondrial inner membrane protein translocase of trypanosomes" in Molecular Microbiology.

All mitochondria import >95% of their proteins from the cytosol. This process is mediated by protein translocases in the mitochondrial membranes, whose subunits are generally highly conserved. Most eukaryotes have two inner membrane protein translocases (TIMs) that are specialized to import either presequence-containing or mitochondrial carrier proteins. In contrast, the parasitic protozoan Trypanosoma brucei has a single TIM complex consisting of one conserved and five unique subunits. Here, we identify candidates for new subunits of the TIM or the presequence translocase-associated motor (PAM) using a protein-protein interaction network of previously characterized TIM and PAM subunits. This analysis reveals that the trypanosomal TIM complex contains an additional trypanosomatid-specific subunit, designated TbTim15. TbTim15 is associated with the TIM complex, lacks transmembrane domains, and localizes to the intermembrane space. TbTim15 is essential for procyclic and bloodstream forms of trypanosomes. It contains two twin CX9C motifs and mediates import of both presequence-containing and mitochondrial carrier proteins. While the precise function of TbTim15 in mitochondrial protein import is unknown, our results are consistent with the notion that it may function as an import receptor for the non-canonical trypanosomal TIM complex.

Read the Article in Molecular Microbiology

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Abstract, figure and title from von Känel et al (2024) Mol Microbiol published under a CC BY-NC 4.0 license.