bims-tricox 2025-06-01 papers

Issue of 2025–06–01
two papers selected by
Yash Verma, University of Zurich

Biomolecules. 2025 May 10. pii: 695. [Epub ahead of print]15(5):

The Insertion Domain of Mti2 Facilitates the Association of Mitochondrial Initiation Factors with Mitoribosomes in Schizosaccharomyces pombe.

Ying Luo, Jürg Bähler, Ying Huang.

Translation initiation in mitochondria involves unique mechanisms distinct from those in the cytosol or in bacteria. The Schizosaccharomyces pombe mitochondrial translation initiation factor 2 (Mti2) is the ortholog of human MTIF2, which plays a vital role in synthesizing proteins in mitochondria. Here, we investigate the insertion domain of Mti2, which stabilizes its interaction with the ribosome and is crucial for efficient translation initiation. Our results show that the insertion domain is critical for the proper folding and function of Mti2. The absence of the insertion domain disrupts cell growth and affects the expression of genes encoded by mitochondrial DNA. Additionally, we show that Mti2 physically interacts with the small subunits of mitoribosomes (mtSSU), and deletion of the insertion domain dissociates mitochondrial initiation factors from the mitoribosome, reducing the efficiency of mitochondrial translation. Altogether, these findings highlight the conserved role of the insertion domain in facilitating translation initiation in fission yeast and thus reveal shared principles of mitochondrial translation initiation in both fission yeast and humans.

Keywords: fission yeast; insertion domain; mitochondrial translation; translation initiation factor

DOI: https://doi.org/10.3390/biom15050695

J Mol Biol. 2025 May 23. pii: S0022-2836(25)00295-5. [Epub ahead of print] 169229

Immunoproteasome-specific subunit alterations as a potential therapeutic target for mitochondriopathies.

Agata Kodroń, Konrad Kowalski, Ben Hur Marins Mussulini, Cem Hazir, Mayra A Borrero-Landazabal, Sonia Ngati, Michal Wasilewski, Agnieszka Chacinska.

Mitochondria are double-membrane organelles crucial for eukaryotic cells due to their role in ATP production by oxidative phosphorylation (OXPHOS). Most of the ∼1500 proteins of the mitochondrial proteome are encoded in the nuclear genome, synthesized in the cytosol, and actively transported into mitochondria. The proteasome, a major cellular proteolytic machinery, plays an important role in the quality control of their transport by degradation of inefficiently imported mitochondrial proteins in the cytosol. Proteasome inhibition by bortezomib was described as a strategy to alleviate deficiencies stemming from an inefficient import of proteins into the mitochondria. Notably, an impairment of the respiratory complexes was shown to induce a rearrangement of the proteasome composition to incorporate some of the immunoproteasome catalytic subunits, such as PSMB9. In this study, we demonstrated that targeting immunoproteasome inhibited degradation, and thus restored the abundance of inefficiently imported respiratory complex IV proteins in the patient derived fibroblasts. Furthermore, we demonstrated that the immunoproteasome-specific inhibitors displayed a decreased toxicity compared to bortezomib. Our results indicate that immunoproteasome subunits present a novel molecular target for future therapies of mitochondriopathies.

Keywords: PSMB9; immunoproteasome inhibitors; immunoproteasome subunits; mitochondria; mitochondrial diseases

DOI: https://doi.org/10.1016/j.jmb.2025.169229