bims-tricox 2025-09-07 papers

Issue of 2025–09–07
three papers selected by
Yash Verma, University of Zurich

J Cell Sci. 2025 Aug 15. pii: jcs263694. [Epub ahead of print]138(16):

Insights into the translational activation mechanisms of the COX1 mRNA in yeast mitochondria.

Angelica Zamudio-Ochoa, Yolanda Camacho-Villasana, Ulrik Pedroza-Dávila, Aldo E García-Guerrero, Xochitl Pérez-Martínez.

Mitochondrial translation is a crucial regulatory step in mitochondrial genome expression. In Saccharomyces cerevisiae, translational activators are believed to bind to the 5' UTRs of their target mRNAs to position the mitochondrial ribosome at the start codon. Pet309 and Mss51 are translational activators of COX1 mRNA, which encodes subunit one of cytochrome c oxidase. Pet309 physically interacts with COX1 mRNA, but no direct interaction of Mss51 with its target mRNA has been detected. Currently, the mechanisms underlying translational activation of COX1, or any other mitochondrial gene, remain poorly understood. To explore in depth the mechanism of COX1 mRNA translational activation, we studied the association of Pet309 and Mss51 with the mitochondrial ribosome. Both Pet309 and Mss51 interact with the mitoribosome regardless of the presence of COX1 mRNA or of each other. The association of Pet309 with the ribosome and with COX1 mRNA depends on its N-terminal domain. These findings indicate that Pet309 and Mss51 stably interact with the mitoribosome independently of active translation. By integrating our data with previously published research, we propose a new mechanism of COX1 mRNA translation activation.

Keywords: COX1 mRNA; Mitochondria; Mitoribosome; Mss51; Pet309; Translation

DOI: https://doi.org/10.1242/jcs.263694

Nat Struct Mol Biol. 2025 Aug 28.

Dynamic TOM-TIM23 supercomplex directs mitochondrial protein translocation and sorting.

Yuqi Yang, Shanshan Wang, Guopeng Wang, Yuke Lian, Lingfeng Xue, Wenhong Jiang, Qiang Guo, Chen Song, Long Li.

The mitochondrial translocase of the outer membrane (TOM) and translocase of the inner membrane 23 (TIM23) complexes are coupled to control protein import across the outer and inner membranes, respectively. However, the mechanisms of protein recognition and sorting in the TOM-TIM23 pathway remain unclear. Here we report cryo-electron microscopy structures of a translocating polypeptide substrate captured in the active TOM-TIM23 supercomplex from Saccharomyces cerevisiae. In the TOM complex, the polypeptide substrate adopts multiple conformations stabilized by hydrophilic residues from distinct regions of the Tom40 channel. In the TIM23 complex, the Tim17 and Mgr2 subunits create the translocation pathway, with a central restriction formed by four highly conserved hydrophobic residues. The substrate primarily interacts with hydrophobic residues along the Tim17-Mgr2 pathway. Substrate hydrophobicity modulates the association of Mgr2 with Tim17, enabling dynamic regulation of protein sorting toward either the matrix or membrane. These findings reveal a sophisticated translocation mechanism of the TOM-TIM23 supercomplex that ensures the efficient import of diverse mitochondrial proteins.

DOI: https://doi.org/10.1038/s41594-025-01662-x

Biochemistry (Mosc). 2025 Aug;90(8): 1099-1115

Ribosome in Baker's Yeast Mitochondria are Heterogeneous.

Rinat A Khannanov, Ivan V Chicherin, Mariya V Baleva, Sergey A Levitskii, Ruslan A Vasilev, Ulyana E Piunova, Petr A Kamenski.

Ribosomes are macromolecular machines of conveyor type, which move along the mRNA from triplet to triplet and polymerize cognate amino acids. They are regarded as uniform entities with constant molecular composition bearing no regulatory capacity. However, their ability to interact with multiple proteins involved in translation suggests existence of specialized ribosomes dedicated to biosynthesis of particular proteins. This can be easily imagined in yeast mitochondria, whose genomes encode eight polypeptides, and where protein-specific translation is already represented by translational activators - a group of proteins each regulating a single mRNA translation. Despite this, the subject remains poorly investigated. We report an exploratory approach to search for distinct populations of ribosomes in the yeast mitochondria. Affinity tags were added to mitochondrial ribosomal proteins, ribosomes were isolated by immunoprecipitation and their protein and RNA content was characterized. It was shown that the mitochondrial ribosomes isolated from yeast strains bearing affinity tags on different ribosomal proteins recover different sets of components. The differences were rather quantitative than qualitative, because almost full sets of mitochondrial ribosomal proteins were identified in each sample, but the ratios demonstrated variance ranging from 10 to less than 0.05 molecules per ribosome. In addition, we explored the power of translational activators as a bait to recover ribosomes translating specific mRNAs in yeast mitochondria.

Keywords: mitochondria; ribosome; translation

DOI: https://doi.org/10.1134/S0006297925602047