bims-mitpro 2024-04-21 papers

Issue of 2024‒04‒21
four papers selected by
Andreas Kohler, Umeå University

J Cell Biol. 2024 May 06. pii: e202403190. [Epub ahead of print]223(5):

OMA1 clears traffic jam in TOM tunnel in mammals.

Using an engineered mitochondrial clogger, Krakowczyk et al. (https://doi.org/10.1083/jcb.202306051) identified the OMA1 protease as a critical component that eliminates import failure at the TOM translocase in mammalian cells, providing a novel quality control mechanism that is distinct from those described in yeast.

DOI: https://doi.org/10.1083/jcb.202403190

Mol Microbiol. 2024 Apr 15.

Intermembrane space-localized TbTim15 is an essential subunit of the single mitochondrial inner membrane protein translocase of trypanosomes.

Corinne von Känel, Silke Oeljeklaus, Christoph Wenger, Philip Stettler, Anke Harsman, Bettina Warscheid, André Schneider.

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.

Keywords: Cx9X motifs; TIM complex; Trypanosomes; intermembrane space; mitochondrial protein import

DOI: https://doi.org/10.1111/mmi.15262

Nat Commun. 2024 Apr 16. 15(1): 3286

Bacterial peptidoglycan acts as a digestive signal mediating host adaptation to diverse food resources in C. elegans.

Fanrui Hao, Huimin Liu, Bin Qi.

Food availability and usage is a major adaptive force for the successful survival of animals in nature, yet little is known about the specific signals that activate the host digestive system to allow for the consumption of varied foods. Here, by using a food digestion system in C. elegans, we discover that bacterial peptidoglycan (PGN) is a unique food signal that activates animals to digest inedible food. We identified that a glycosylated protein, Bacterial Colonization Factor-1 (BCF-1), in the gut interacts with bacterial PGN, leading to the inhibition of the mitochondrial unfolded protein response (UPRmt) by regulating the release of Neuropeptide-Like Protein (NLP-3). Interestingly, activating UPRmt was found to hinder food digestion, which depends on the innate immune p38 MAPK/PMK-1 pathway. Conversely, inhibiting PMK-1 was able to alleviate digestion defects in bcf-1 mutants. Furthermore, we demonstrate that animals with digestion defects experience reduced natural adaptation capabilities. This study reveals that PGN-BCF-1 interaction acts as "good-food signal" to promote food digestion and animal growth, which facilitates adaptation of the host animals by increasing ability to consume a wide range of foods in their natural environment.

DOI: https://doi.org/10.1038/s41467-024-47530-y

Biochem Soc Trans. 2024 Apr 17. pii: BST20231236. [Epub ahead of print]

New insights into the structure and dynamics of the TOM complex in mitochondria.

Stephan Nussberger, Robin Ghosh, Shuo Wang.

To date, there is no general physical model of the mechanism by which unfolded polypeptide chains with different properties are imported into the mitochondria. At the molecular level, it is still unclear how transit polypeptides approach, are captured by the protein translocation machinery in the outer mitochondrial membrane, and how they subsequently cross the entropic barrier of a protein translocation pore to enter the intermembrane space. This deficiency has been due to the lack of detailed structural and dynamic information about the membrane pores. In this review, we focus on the recently determined sub-nanometer cryo-EM structures and our current knowledge of the dynamics of the mitochondrial two-pore outer membrane protein translocation machinery (TOM core complex), which provide a starting point for addressing the above questions. Of particular interest are recent discoveries showing that the TOM core complex can act as a mechanosensor, where the pores close as a result of interaction with membrane-proximal structures. We highlight unusual and new correlations between the structural elements of the TOM complexes and their dynamic behavior in the membrane environment.

Keywords: Tom complex; electron cryo-microscopy; mechanosensitivity; mitochondria; protein translocation; single-molecule microscopy

DOI: https://doi.org/10.1042/BST20231236